Scholars@Duke
Smita K Nair

Smita K Nair

Professor in Surgery
Surgery, Surgical Sciences
Box 103035 Medical Center, Durham, NC 27710
Room 1077, MSRB-2, 106 Research Drive, Durham, NC 27710
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Selected Publications

Peripheral blood interferon responses to toll-like receptor 1/2 signaling associate with longer survival in men with metastatic prostate cancer treated with Sipleucel-T.

Journal Article Cancer Res Commun · September 25, 2024 Mounting evidence links systemic innate immunity with cancer immune surveillance. In advanced metastatic castration resistant prostate cancer (mCRPC), Black patients have been found to have increased inflammatory markers and longer survival after sipuleuce ... Full text Link to item Cite

Cancer mRNA vaccines: clinical advances and future opportunities.

Journal Article Nat Rev Clin Oncol · July 2024 mRNA vaccines have been revolutionary in terms of their rapid development and prevention of SARS-CoV-2 infections during the COVID-19 pandemic, and this technology has considerable potential for application to the treatment of cancer. Compared with traditi ... Full text Link to item Cite

Expression profiling of cell cycle regulatory genes E2F and CDKA during early stages of zygotic embryo culture in coconut (Cocos nucifera L.)

Journal Article Plant Cell, Tissue and Organ Culture · December 1, 2023 Coconut (Cocos nucifera L.) is known to be highly recalcitrant to in vitro manipulations. The current study was conducted to comprehend the impact of different plant growth regulators (PGRs) on the early in vitro response of coconut embryos. The zygotic em ... Full text Cite

Transcriptional and epigenetic regulators of human CD8+ T cell function identified through orthogonal CRISPR screens.

Journal Article Nat Genet · December 2023 Clinical response to adoptive T cell therapies is associated with the transcriptional and epigenetic state of the cell product. Thus, discovery of regulators of T cell gene networks and their corresponding phenotypes has potential to improve T cell therapi ... Full text Link to item Cite

One-step Reverse Transcription-LoopMediated Isothermal Amplification (RT-LAMP) for closed-tube colorimetric detection of banana bract mosaic virus in Banana (Musa spp.)

Journal Article 3 Biotech · May 1, 2023 The banana bract mosaic virus (BBrMV) is a major virus affecting bananas and plantains. Banana being propagated vegetatively, there arises a high risk of virus transmission through planting materials. Available molecular detection technique like the Revers ... Full text Cite

Intratumor childhood vaccine-specific CD4+ T-cell recall coordinates antitumor CD8+ T cells and eosinophils.

Journal Article J Immunother Cancer · April 2023 BACKGROUND: Antitumor mechanisms of CD4+ T cells remain crudely defined, and means to effectively harness CD4+ T-cell help for cancer immunotherapy are lacking. Pre-existing memory CD4+ T cells hold potential to be leveraged for this purpose. Moreover, the ... Full text Link to item Cite

Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models.

Journal Article Sci Transl Med · February 8, 2023 D2C7-immunotoxin (IT), a dual-specific IT targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, demonstrates encouraging survival outcomes in a subset of patients with glioblastoma. We hypothesized tha ... Full text Link to item Cite

Functional reprogramming of peripheral blood monocytes by soluble mediators in patients with pancreatic cancer and intraductal papillary mucinous neoplasms.

Journal Article Front Immunol · 2023 BACKGROUND: Monocytes and monocyte-derived tumor infiltrating cells have been implicated in the immunosuppression and immune evasion associated with pancreatic adenocarcinoma (PDAC). Yet, precisely how monocytes in the periphery and tumor microenvironment ... Full text Link to item Cite

The Quest for mRNA Vaccines.

Journal Article Nucleic Acid Ther · December 2022 The success of mRNA vaccines against COVID-19 is nothing short of a medical revolution. Given its chemical lability the use of mRNA as a therapeutic has been counterintuitive and met with skepticism. The development of mRNA-based COVID-19 vaccines was the ... Full text Link to item Cite

Age and Comorbidities Predict COVID-19 Outcome, Regardless of Innate Immune Response Severity: A Single Institutional Cohort Study.

Journal Article Crit Care Explor · December 2022 UNLABELLED: The COVID-19 pandemic has claimed over eight hundred thousand lives in the United States alone, with older individuals and those with comorbidities being at higher risk of severe disease and death. Although severe acute respiratory syndrome cor ... Full text Link to item Cite

Multidimensional Immunophenotyping of Intraductal Papillary Mucinous Neoplasms Reveals Novel T Cell and Macrophage Signature.

Conference Ann Surg Oncol · November 2022 BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) are the only radiographically identifiable precursor to pancreatic adenocarcinoma, yet little is known about how these lesions progress to cancer. Inflammation has been associated with dysplastic ... Full text Link to item Cite

Ethanol Ablation Therapy Drives Immune-Mediated Antitumor Effects in Murine Breast Cancer Models.

Journal Article Cancers (Basel) · September 25, 2022 Ethanol ablation is a minimally invasive, cost-effective method of destroying tumor tissue through an intratumoral injection of high concentrations of cytotoxic alcohol. Ethyl-cellulose ethanol (ECE) ablation, a modified version of ethanol ablation, contai ... Full text Link to item Cite

Colorimetric detection platform for banana bunchy top virus (BBTV) based on closed-tube loop mediated isothermal amplification (LAMP) assay

Journal Article VirusDisease · September 1, 2022 A colorimetric closed-tube Loop mediated isothermal amplification (LAMP) assay was developed for rapid and sensitive detection of banana bunchy top virus (BBTV) from leaf and sucker tissues of infected banana plants. Six LAMP primers were designed targetin ... Full text Cite

Multimodality analysis confers a prognostic benefit of a T-cell infiltrated tumor microenvironment and peripheral immune status in patients with melanoma.

Journal Article J Immunother Cancer · September 2022 BACKGROUND: We previously reported results from a phase 1 study testing intratumoral recombinant poliovirus, lerapolturev, in 12 melanoma patients. All 12 patients received anti-PD-1 systemic therapy before lerapolturev, and 11 of these 12 patients also re ... Full text Link to item Cite

Intravital optical imaging for immune cell tracking after photoimmunotherapy with plasmonic gold nanostars.

Journal Article Nanotechnology · August 31, 2022 Bladder cancer has been ranked as one of the most commonly occurring cancers in men and women with approximately half of the diagnoses being the late stage and/or metastatic diseases. We have developed a novel cancer treatment by combining gold nanostar-me ... Full text Link to item Cite

Targeting Tumor Acidosis and Regulatory T Cells Unmasks Anti-Metastatic Potential of Local Tumor Ablation in Triple-Negative Breast Cancer.

Journal Article Int J Mol Sci · July 30, 2022 Triple-negative breast cancer (TNBC) is an immunologically heterogenous disease that lacks clinically actionable targets and is more likely to progress to metastatic disease than other types of breast cancer. Tumor ablation has been used to increase respon ... Full text Link to item Cite

Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study.

Journal Article Anesthesiology · July 1, 2022 BACKGROUND: COVID-19 causes hypercoagulability, but the association between coagulopathy and hypoxemia in critically ill patients has not been thoroughly explored. This study hypothesized that severity of coagulopathy would be associated with acute respira ... Full text Link to item Cite

Polyethylene Glycol-Like Brush Polymer Conjugate of a Protein Drug Does Not Induce an Antipolymer Immune Response and Has Enhanced Pharmacokinetics than Its Polyethylene Glycol Counterpart.

Journal Article Adv Sci (Weinh) · April 2022 Protein therapeutics, except for antibodies, have a short plasma half-life and poor stability in circulation. Covalent coupling of polyethylene glycol (PEG) to protein drugs addresses this limitation. However, unlike previously thought, PEG is immunogenic. ... Full text Link to item Cite

Peripheral blood interferon responses to toll-like receptor 1/2 signaling associate with longer survival in men with metastatic prostate cancer treated with Sipleucel-T.

Journal Article Cancer Res Commun · September 25, 2024 Mounting evidence links systemic innate immunity with cancer immune surveillance. In advanced metastatic castration resistant prostate cancer (mCRPC), Black patients have been found to have increased inflammatory markers and longer survival after sipuleuce ... Full text Link to item Cite

Cancer mRNA vaccines: clinical advances and future opportunities.

Journal Article Nat Rev Clin Oncol · July 2024 mRNA vaccines have been revolutionary in terms of their rapid development and prevention of SARS-CoV-2 infections during the COVID-19 pandemic, and this technology has considerable potential for application to the treatment of cancer. Compared with traditi ... Full text Link to item Cite

Expression profiling of cell cycle regulatory genes E2F and CDKA during early stages of zygotic embryo culture in coconut (Cocos nucifera L.)

Journal Article Plant Cell, Tissue and Organ Culture · December 1, 2023 Coconut (Cocos nucifera L.) is known to be highly recalcitrant to in vitro manipulations. The current study was conducted to comprehend the impact of different plant growth regulators (PGRs) on the early in vitro response of coconut embryos. The zygotic em ... Full text Cite

Transcriptional and epigenetic regulators of human CD8+ T cell function identified through orthogonal CRISPR screens.

Journal Article Nat Genet · December 2023 Clinical response to adoptive T cell therapies is associated with the transcriptional and epigenetic state of the cell product. Thus, discovery of regulators of T cell gene networks and their corresponding phenotypes has potential to improve T cell therapi ... Full text Link to item Cite

One-step Reverse Transcription-LoopMediated Isothermal Amplification (RT-LAMP) for closed-tube colorimetric detection of banana bract mosaic virus in Banana (Musa spp.)

Journal Article 3 Biotech · May 1, 2023 The banana bract mosaic virus (BBrMV) is a major virus affecting bananas and plantains. Banana being propagated vegetatively, there arises a high risk of virus transmission through planting materials. Available molecular detection technique like the Revers ... Full text Cite

Intratumor childhood vaccine-specific CD4+ T-cell recall coordinates antitumor CD8+ T cells and eosinophils.

Journal Article J Immunother Cancer · April 2023 BACKGROUND: Antitumor mechanisms of CD4+ T cells remain crudely defined, and means to effectively harness CD4+ T-cell help for cancer immunotherapy are lacking. Pre-existing memory CD4+ T cells hold potential to be leveraged for this purpose. Moreover, the ... Full text Link to item Cite

Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models.

Journal Article Sci Transl Med · February 8, 2023 D2C7-immunotoxin (IT), a dual-specific IT targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, demonstrates encouraging survival outcomes in a subset of patients with glioblastoma. We hypothesized tha ... Full text Link to item Cite

Functional reprogramming of peripheral blood monocytes by soluble mediators in patients with pancreatic cancer and intraductal papillary mucinous neoplasms.

Journal Article Front Immunol · 2023 BACKGROUND: Monocytes and monocyte-derived tumor infiltrating cells have been implicated in the immunosuppression and immune evasion associated with pancreatic adenocarcinoma (PDAC). Yet, precisely how monocytes in the periphery and tumor microenvironment ... Full text Link to item Cite

The Quest for mRNA Vaccines.

Journal Article Nucleic Acid Ther · December 2022 The success of mRNA vaccines against COVID-19 is nothing short of a medical revolution. Given its chemical lability the use of mRNA as a therapeutic has been counterintuitive and met with skepticism. The development of mRNA-based COVID-19 vaccines was the ... Full text Link to item Cite

Age and Comorbidities Predict COVID-19 Outcome, Regardless of Innate Immune Response Severity: A Single Institutional Cohort Study.

Journal Article Crit Care Explor · December 2022 UNLABELLED: The COVID-19 pandemic has claimed over eight hundred thousand lives in the United States alone, with older individuals and those with comorbidities being at higher risk of severe disease and death. Although severe acute respiratory syndrome cor ... Full text Link to item Cite

Multidimensional Immunophenotyping of Intraductal Papillary Mucinous Neoplasms Reveals Novel T Cell and Macrophage Signature.

Conference Ann Surg Oncol · November 2022 BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) are the only radiographically identifiable precursor to pancreatic adenocarcinoma, yet little is known about how these lesions progress to cancer. Inflammation has been associated with dysplastic ... Full text Link to item Cite

Ethanol Ablation Therapy Drives Immune-Mediated Antitumor Effects in Murine Breast Cancer Models.

Journal Article Cancers (Basel) · September 25, 2022 Ethanol ablation is a minimally invasive, cost-effective method of destroying tumor tissue through an intratumoral injection of high concentrations of cytotoxic alcohol. Ethyl-cellulose ethanol (ECE) ablation, a modified version of ethanol ablation, contai ... Full text Link to item Cite

Colorimetric detection platform for banana bunchy top virus (BBTV) based on closed-tube loop mediated isothermal amplification (LAMP) assay

Journal Article VirusDisease · September 1, 2022 A colorimetric closed-tube Loop mediated isothermal amplification (LAMP) assay was developed for rapid and sensitive detection of banana bunchy top virus (BBTV) from leaf and sucker tissues of infected banana plants. Six LAMP primers were designed targetin ... Full text Cite

Multimodality analysis confers a prognostic benefit of a T-cell infiltrated tumor microenvironment and peripheral immune status in patients with melanoma.

Journal Article J Immunother Cancer · September 2022 BACKGROUND: We previously reported results from a phase 1 study testing intratumoral recombinant poliovirus, lerapolturev, in 12 melanoma patients. All 12 patients received anti-PD-1 systemic therapy before lerapolturev, and 11 of these 12 patients also re ... Full text Link to item Cite

Intravital optical imaging for immune cell tracking after photoimmunotherapy with plasmonic gold nanostars.

Journal Article Nanotechnology · August 31, 2022 Bladder cancer has been ranked as one of the most commonly occurring cancers in men and women with approximately half of the diagnoses being the late stage and/or metastatic diseases. We have developed a novel cancer treatment by combining gold nanostar-me ... Full text Link to item Cite

Targeting Tumor Acidosis and Regulatory T Cells Unmasks Anti-Metastatic Potential of Local Tumor Ablation in Triple-Negative Breast Cancer.

Journal Article Int J Mol Sci · July 30, 2022 Triple-negative breast cancer (TNBC) is an immunologically heterogenous disease that lacks clinically actionable targets and is more likely to progress to metastatic disease than other types of breast cancer. Tumor ablation has been used to increase respon ... Full text Link to item Cite

Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study.

Journal Article Anesthesiology · July 1, 2022 BACKGROUND: COVID-19 causes hypercoagulability, but the association between coagulopathy and hypoxemia in critically ill patients has not been thoroughly explored. This study hypothesized that severity of coagulopathy would be associated with acute respira ... Full text Link to item Cite

Polyethylene Glycol-Like Brush Polymer Conjugate of a Protein Drug Does Not Induce an Antipolymer Immune Response and Has Enhanced Pharmacokinetics than Its Polyethylene Glycol Counterpart.

Journal Article Adv Sci (Weinh) · April 2022 Protein therapeutics, except for antibodies, have a short plasma half-life and poor stability in circulation. Covalent coupling of polyethylene glycol (PEG) to protein drugs addresses this limitation. However, unlike previously thought, PEG is immunogenic. ... Full text Link to item Cite

DAMPs/PAMPs induce monocytic TLR activation and tolerance in COVID-19 patients; nucleic acid binding scavengers can counteract such TLR agonists.

Journal Article Biomaterials · April 2022 Millions of COVID-19 patients have succumbed to respiratory and systemic inflammation. Hyperstimulation of toll-like receptor (TLR) signaling is a key driver of immunopathology following infection by viruses. We found that severely ill COVID-19 patients in ... Full text Open Access Link to item Cite

The In Vitro Differentiation of Human CD141+CLEC9A+ Dendritic Cells from Mobilized Peripheral Blood CD34+ Hematopoietic Stem Cells.

Journal Article Curr Protoc · April 2022 As shown in various preclinical studies, conventional type-1 dendritic cells, or cDC1s, play a critical role in the immunological rejection of tumors and in the defense against pathogens. This indispensability stems from their potent capacity to activate c ... Full text Link to item Cite

Intratumoral delivery of brachytherapy and immunotherapy by a thermally triggered polypeptide depot.

Journal Article J Control Release · March 2022 Biomaterial-based approaches for a combination of radiotherapy and immunotherapy can improve outcomes in metastatic cancer through local delivery of both therapeutic modalities to the primary tumor to control local tumor growth and distant metastases. This ... Full text Link to item Cite

Oncolytic viruses in melanoma.

Journal Article Front Biosci (Landmark Ed) · February 14, 2022 Malignant melanoma recurrence remains heterogeneous in presentation, ranging from locoregional disease (i.e., local recurrence, satellites, in transit disease) to distant dermal and visceral metastases. This diverse spectrum of disease requires a personali ... Full text Link to item Cite

β-Cyclodextrin-containing polymer treatment of cutaneous lupus and influenza improves outcomes.

Journal Article Mol Ther · February 2, 2022 Nucleic acid (NA)-containing damage- and pathogen-associated molecular patterns (DAMPs and PAMPs, respectively) are implicated in numerous pathological conditions from infectious diseases to autoimmune disorders. Nucleic acid-binding polymers, including po ... Full text Link to item Cite

Generation of Tumor Targeted Dendritic Cell Vaccines with Improved Immunogenic and Migratory Phenotype.

Journal Article Methods in molecular biology (Clifton, N.J.) · January 2022 Our group has employed methodologies for effective ex vivo generation of dendritic cell (DC) vaccines for patients with primary malignant brain tumors. In order to reliably produce the most potent, most representational vaccinated DC that will engender an ... Full text Cite

Spatial biology analysis reveals B cell follicles in secondary lymphoid structures may regulate anti-tumor responses at initial melanoma diagnosis.

Journal Article Front Immunol · 2022 INTRODUCTION: B cells are key regulators of immune responses in melanoma. We aimed to explore differences in the histologic location and activation status of B cell follicles in sentinel lymph nodes (SLN) of melanoma patients. METHODS: Flow cytometry was p ... Full text Link to item Cite

Omics research for crop improvement in spices

Chapter · January 1, 2022 In the scenario of increasing global population and changing climatic conditions, breeding approaches in crops need to be integrated with novel technologies for enhancing yield, quality, and resistance to biotic/abiotic stresses. The international trade de ... Full text Cite

Breast cancer-derived DAMPs enhance cell invasion and metastasis, while nucleic acid scavengers mitigate these effects.

Journal Article Molecular therapy. Nucleic acids · December 2021 Breast cancer (BC) is the most common malignancy in women. Particular subtypes with aggressive behavior are major contributors to poor outcomes. Triple-negative breast cancer (TNBC) is difficult to treat, pro-inflammatory, and highly metastatic. We demonst ... Full text Cite

Plasmonic gold nanostars for synergistic photoimmunotherapy to treat cancer.

Journal Article Nanophotonics · September 2021 Cancer is the second leading cause of death and there is an urgent need to improve cancer management. We have developed an innovative cancer therapy named Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) by combining gold nanostars (GNS)-mediated pho ... Full text Open Access Link to item Cite

Characterization of Sentinel Lymph Node Immune Signatures and Implications for Risk Stratification for Adjuvant Therapy in Melanoma.

Journal Article Ann Surg Oncol · July 2021 BACKGROUND: Although sentinel lymph node (SLN) biopsy is a standard procedure used to identify patients at risk for melanoma recurrence, it fails to risk-stratify certain patients accurately. Because processes in SLNs regulate anti-tumor immune responses, ... Full text Link to item Cite

Multiplexed, quantitative serological profiling of COVID-19 from blood by a point-of-care test.

Journal Article Sci Adv · June 2021 Highly sensitive, specific, and point-of-care (POC) serological assays are an essential tool to manage coronavirus disease 2019 (COVID-19). Here, we report on a microfluidic POC test that can profile the antibody response against multiple severe acute resp ... Full text Link to item Cite

Resetting the tumor microenvironment to favor anti-tumor immunity after local ablation.

Conference Journal of Clinical Oncology · May 20, 2021 2561 Background: Percutaneous tumor ablation is a non-surgical method of tumor destruction that leaves necrotic tumor debris in situ. Tumor associated antigens released after ablation have the potential to initiate a systemic ant ... Full text Cite

Controlling cancer-induced inflammation with a nucleic acid scavenger prevents lung metastasis in murine models of breast cancer.

Journal Article Mol Ther · May 5, 2021 Tumor cells release nucleic acid-containing proinflammatory complexes, termed nucleic acid-containing damage-associated molecular patterns (NA DAMPs), passively upon death and actively during stress. NA DAMPs activate pattern recognition receptors on cells ... Full text Link to item Cite

Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma.

Journal Article J Immunother Cancer · April 2021 BACKGROUND: While programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) antagonists have improved the prognosis for many patients with melanoma, around 60% fail therapy. PVSRIPO is a non-neurovirulent rhinovirus:poliovirus chimera th ... Full text Link to item Cite

Key Pathogenic Factors in Coronavirus Disease 2019-Associated Coagulopathy and Acute Lung Injury Highlighted in a Patient With Copresentation of Acute Myelocytic Leukemia: A Case Report.

Journal Article A A Pract · March 30, 2021 The role of concurrent illness in coronavirus disease 2019 (COVID-19) is unknown. Patients with leukemia may display altered thromboinflammatory responses. We report a 53-year-old man presenting with acute leukemia and COVID-19 who developed thrombotic com ... Full text Open Access Link to item Cite

Viral infection of cells within the tumor microenvironment mediates antitumor immunotherapy via selective TBK1-IRF3 signaling.

Journal Article Nat Commun · March 25, 2021 Activating intra-tumor innate immunity might enhance tumor immune surveillance. Virotherapy is proposed to achieve tumor cell killing, while indirectly activating innate immunity. Here, we report that recombinant poliovirus therapy primarily mediates antit ... Full text Link to item Cite

Abstract P102: Elevated Von Willebrand Factor in Patients Presenting With Large-Vessel Occlusion Stroke as First Symptom of COVID-19 Mirrors Levels in Patients With COVID-19 Requiring ICU-Level Care

Conference Stroke · March 2021 Introduction: COVID-19 is a coagulopathic disease marked by elevated d-dimers, fibrinogen, and von Willebrand factor (vWF) levels accompanying arterial and venous thrombosis. While the majority of thr ... Full text Cite

Dissecting the immune landscape of tumor draining lymph nodes in melanoma with high-plex spatially resolved protein detection.

Journal Article Cancer Immunol Immunother · February 2021 BACKGROUND: In melanoma patients, microscopic tumor in the sentinel lymph-node biopsy (SLN) increases the risk of distant metastases, but the transition from tumor in the SLN to metastatic disease remains poorly understood. METHODS: Fluorescent staining fo ... Full text Link to item Cite

A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope.

Journal Article NPJ Vaccines · January 18, 2021 Personalized cancer vaccines targeting neoantigens arising from somatic missense mutations are currently being evaluated for the treatment of various cancers due to their potential to elicit a multivalent, tumor-specific immune response. Several cancers ex ... Full text Open Access Link to item Cite

Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.

Journal Article Nat Commun · January 13, 2021 Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10-20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunother ... Full text Open Access Link to item Cite

Multiplexed, quantitative serological profiling of COVID-19 from a drop of blood by a point-of-care test.

Journal Article medRxiv · November 7, 2020 Highly sensitive, specific, and point-of-care (POC) serological assays are an essential tool to manage the COVID-19 pandemic. Here, we report on a microfluidic, multiplexed POC test that can profile the antibody response against multiple SARS-CoV-2 antigen ... Full text Link to item Cite

Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses.

Journal Article J Clin Invest · February 3, 2020 Efficacy of dendritic cell (DC) cancer vaccines is classically thought to depend on their antigen-presenting cell (APC) activity. Studies show, however, that DC vaccine priming of cytotoxic T lymphocytes (CTLs) requires the activity of endogenous DCs, sugg ... Full text Link to item Cite

Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity.

Journal Article Nat Commun · January 27, 2020 Viruses naturally engage innate immunity, induce antigen presentation, and mediate CD8 T cell priming against foreign antigens. Polioviruses can provide a context optimal for generating antigen-specific CD8 T cells, as they have natural tropism for dendrit ... Full text Link to item Cite

Oncolytic poliovirus immunotherapy for breast cancer

Conference JOURNAL OF IMMUNOLOGY · 2020 Cite

Immune expression in children with Wilms tumor: a pilot study.

Journal Article J Pediatr Urol · October 2019 BACKGROUND: Given improvements in multimodality therapy, survival among children with Wilms tumor (WT) exceeds 90%. However, 15% of children with favorable histology and 50% of children with anaplastic WT experience recurrence or progression. Of patients w ... Full text Link to item Cite

Abstract 4515: Utilizing nucleic-acid scavengers (NASs) to inhibit proinflammatory and proinvasive signaling in triple-negative breast cancer

Conference Cancer Research · July 1, 2019 AbstractBreast cancers (BC) remain the most lethal malignancies amongst women worldwide and the second leading cause of cancer-related mortalities in the US. Subtype heterogeneity and aggressive invasive pot ... Full text Cite

Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations.

Journal Article J Immunother Cancer · May 29, 2019 BACKGROUND: D2C7-IT is a novel immunotoxin (IT) targeting wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins in glioblastoma. In addition to inherent tumoricidal activity, immunotoxins induce secondary immun ... Full text Open Access Link to item Cite

Can Exercise-Induced Modulation of the Tumor Physiologic Microenvironment Improve Antitumor Immunity?

Journal Article Cancer Res · May 15, 2019 The immune system plays an important role in controlling cancer growth. However, cancers evolve to evade immune detection. Immune tolerance and active immune suppression results in unchecked cancer growth and progression. A major contributor to immune tole ... Full text Link to item Cite

Examining Peripheral and Tumor Cellular Immunome in Patients With Cancer.

Journal Article Front Immunol · 2019 Immunotherapies are rapidly being integrated into standard of care (SOC) therapy in conjunction with surgery, chemotherapy, and radiotherapy for many cancers and a large number of clinical studies continue to explore immunotherapy alone and as part of comb ... Full text Link to item Cite

Early Stage HER2-Positive Breast Cancers Not Achieving a pCR From Neoadjuvant Trastuzumab- or Pertuzumab-Based Regimens Have an Immunosuppressive Phenotype.

Journal Article Clin Breast Cancer · October 2018 BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) might predict pathologic complete response (pCR) in patients with HER2-positive (HER2+) breast cancer treated with trastuzumab (H). Docetaxel (T), carboplatin (C), H, and pertuzumab (P) have immune- ... Full text Link to item Cite

Abstract A79: Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of antigen-presenting cells and tumor antigen-specific CTLs

Conference Cancer Immunology Research · September 1, 2018 AbstractThe tumor microenvironment favors tumor immune escape by suppressing production, activation and/or function of antitumor T cells. Our group has developed a recombinant Rhino-Poliovirus chimera, PVSRI ... Full text Cite

Recurrent Glioblastoma Treated with Recombinant Poliovirus.

Journal Article N Engl J Med · July 12, 2018 BACKGROUND: The prognosis of patients with recurrent World Health Organization (WHO) grade IV malignant glioma is dismal, and there is currently no effective therapy. We conducted a dose-finding and toxicity study in this population of patients, evaluating ... Full text Link to item Cite

Targeting inflammation to prevent breast cancer metastasis

Conference JOURNAL OF IMMUNOLOGY · May 1, 2018 Link to item Cite

Clinical Profile of Neonates with Hypernatremic Dehydration in an Outborn Neonatal Intensive Care Unit.

Journal Article Indian Pediatr · April 15, 2018 This hospital-record review describes the clinical profile of hypernatremic dehydration in neonates. 49 neonates (3.4% of the total admitted newborns) developed hypernatremic dehydration between January 2014 and August 2015. The major presenting complaints ... Link to item Cite

Research Letters

Journal Article Indian Pediatrics · April 1, 2018 Full text Cite

Recombinant Poliovirus for Cancer Immunotherapy.

Journal Article Annu Rev Med · January 29, 2018 Mechanisms to elicit antiviral immunity, a natural host response to viral pathogen challenge, are of eminent relevance to cancer immunotherapy. "Oncolytic" viruses, naturally existing or genetically engineered viral agents with cell type-specific propagati ... Full text Link to item Cite

Paracrine Wnt5a-β-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization.

Journal Article Immunity · January 16, 2018 Featured Publication Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have des ... Full text Open Access Link to item Cite

Nanoparticle formulation improves doxorubicin efficacy by enhancing host antitumor immunity.

Journal Article J Control Release · January 10, 2018 Strategies that enhance the host antitumor immune response promise to revolutionize cancer therapy. Optimally mobilizing the immune system will likely require a multi-pronged approach to overcome the resistance developed by tumors to therapy. Recently, it ... Full text Link to item Cite

Dendritic Cells Enhance Polyfunctionality of Adoptively Transferred T Cells That Target Cytomegalovirus in Glioblastoma.

Journal Article Cancer Res · January 1, 2018 Median survival for glioblastoma (GBM) remains <15 months. Human cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV antigens as tumor-specific immunotherapy targets. A recen ... Full text Link to item Cite

Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen-specific CTLs.

Journal Article Sci Transl Med · September 20, 2017 Featured Publication Tumors thrive in an immunosuppressive microenvironment that impedes antitumor innate and adaptive immune responses. Thus, approaches that can overcome immunosuppression and engage antitumor immunity are needed. This study defines the adjuvant and cancer im ... Full text Link to item Cite

Long-term Survival in Glioblastoma with Cytomegalovirus pp65-Targeted Vaccination.

Journal Article Clin Cancer Res · April 15, 2017 Featured Publication Purpose: Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can e ... Full text Link to item Cite

A combinatorial immunotherapy for malignant brain tumors: D2C7 immunotoxin and immune checkpoint inhibitors.

Conference Journal of Clinical Oncology · March 1, 2017 102 Background: Immunotoxins can induce direct and rapid cytotoxicity by targeting specific tumor antigens. D2C7 is a unique recombinant immunotoxin targeting EGFRwt/EGFRvIII, two frequently overexpressed proteins on gliomas, and ... Full text Cite

Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models.

Journal Article Oncotarget · November 29, 2016 Intratumoral inoculation of viruses with tumor-selective cytotoxicity may induce cancer cell death and, thereby, shrink neoplastic lesions. It is unlikely, however, that viral tumor cell killing alone could produce meaningful, durable clinical responses, a ... Full text Link to item Cite

The RNAissance period.

Journal Article Discov Med · August 2016 The concept that RNA has played a major role in the evolution of life stems from the "RNA World" hypothesis. This role of RNA was not immediately appreciated. Similarly, the scientific community has just recently begun to recognize the true potential of RN ... Link to item Cite

From the RNA world to the clinic.

Journal Article Science · June 17, 2016 Featured Publication The study of RNA has continually emphasized the structural and functional versatility of RNA molecules. This versatility has inspired translational and clinical researchers to explore the utility of RNA-based therapeutic agents for a wide variety of medica ... Full text Link to item Cite

RNA Vaccination Therapy: Advances in an Emerging Field.

Journal Article J Immunol Res · 2016 Featured Publication Full text Link to item Cite

Transfecting Human Monocytes with RNA.

Journal Article Methods Mol Biol · 2016 Targeting monocytes as a delivery system for drugs or nucleic acids, and thereby harnessing their natural tissue-infiltrating capacity, has become an area of intense investigation in both basic and clinical research. Herein we describe an efficient method ... Full text Link to item Cite

Abstract A157: Oncolytic poliovirus mediated immune events

Journal Article Cancer Immunology Research · January 1, 2016 AbstractIntroduction: Tumor-targeted therapies that efficiently eliminate malignant cells and in the process engage the innate and adaptive immune system are desirable for preventing cancer recurrence. We ha ... Full text Cite

RNA-Mediated Reprogramming of Primary Adult Human Dermal Fibroblasts into c-kit(+) Cardiac Progenitor Cells.

Journal Article Stem Cells Dev · November 15, 2015 Featured Publication Cardiovascular disease is the leading cause of death in the United States. Heart failure is a common, costly, and potentially fatal condition that is inadequately managed by pharmaceuticals. Cardiac repair therapies are promising alternative options. A pot ... Full text Link to item Cite

Ex vivo generation of dendritic cells from cryopreserved, post-induction chemotherapy, mobilized leukapheresis from pediatric patients with medulloblastoma.

Journal Article J Neurooncol · October 2015 Generation of patient-derived, autologous dendritic cells (DCs) is a critical component of cancer immunotherapy with ex vivo-generated, tumor antigen-loaded DCs. An important factor in the ability to generate DCs is the potential impact of prior therapies ... Full text Link to item Cite

RNA in cancer vaccine therapy

Chapter · May 6, 2015 Cite

Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients.

Journal Article Nature · March 19, 2015 Featured Publication After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vacci ... Full text Open Access Link to item Cite

Gene Expression Profile of Dendritic Cell-Tumor Cell Hybrids Determined by Microarrays and Its Implications for Cancer Immunotherapy.

Journal Article J Immunol Res · 2015 BACKGROUND: Dendritic cell- (DC-) tumor fusion cells stimulate effective in vivo antitumor responses. However, therapeutic approaches are dependent upon the coadministration of exogenous 3rd signals. The purpose of this study was to determine the mechanism ... Full text Link to item Cite

RNA-Based Vaccines in Cancer Immunotherapy.

Journal Article J Immunol Res · 2015 RNA vaccines traditionally consist of messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s) of interest. Once administered and internalized by host cells, the mRNA transcripts ... Full text Open Access Link to item Cite

Oncolytic polio virotherapy of cancer.

Journal Article Cancer · November 1, 2014 Featured Publication Recently, the century-old idea of targeting cancer with viruses (oncolytic viruses) has come of age, and promise has been documented in early stage and several late-stage clinical trials in a variety of cancers. Although originally prized for their direct ... Full text Link to item Cite

Messenger RNA (mRNA) nanoparticle tumour vaccination.

Journal Article Nanoscale · July 21, 2014 Use of mRNA-based vaccines for tumour immunotherapy has gained increasing attention in recent years. A growing number of studies applying nanomedicine concepts to mRNA tumour vaccination show that the mRNA delivered in nanoparticle format can generate a mo ... Full text Link to item Cite

RANDOMIZATION OF PATIENTS WITH GLIOBLASTOMA TO VACCINE SITE PRE-CONDITIONING WITH TETANUS-DIPHTHERIA TOXOID SYSTEMICALLY ENHANCES MIGRATION AND THERAPEUTIC EFFECT OF CYTOMEGALOVIRUS PP65-PULSED DENDRITIC CELL VACCINE IN A MIP-1α-DEPENDENT FASHION.

Conference Neuro Oncol · July 2014 Dendritic cell (DC) vaccine efficacy is limited by suboptimal migration to vaccine site-draining lymph nodes (VDLNs). In mice, vaccine site conditioning with inflammatory cytokines or mature DCs increases DC trafficking and the induction of antigen-specifi ... Full text Link to item Cite

Intranasal mRNA nanoparticle vaccination induces prophylactic and therapeutic anti-tumor immunity.

Journal Article Sci Rep · June 4, 2014 Featured Publication Direct in vivo administration of messenger RNA (mRNA) delivered in both naked and nanoparticle formats are actively investigated because the use of dendritic cells transfected ex vivo with mRNA for cancer therapy is expensive and needs significant infrastr ... Full text Link to item Cite

Whole blood cells loaded with messenger RNA as an anti-tumor vaccine.

Journal Article Adv Healthc Mater · June 2014 Featured Publication The use of a cell-based vaccine composed of autologous whole blood cells loaded with mRNA is described. Mice immunized with whole blood cells loaded with mRNA encoding antigen develop anti-tumor immunity comparable to DC-RNA immunization. This approach off ... Full text Link to item Cite

Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells.

Journal Article Clin Cancer Res · May 15, 2014 Featured Publication PURPOSE: Despite aggressive conventional therapy, glioblastoma (GBM) remains uniformly lethal. Immunotherapy, in which the immune system is harnessed to specifically attack malignant cells, offers a treatment option with less toxicity. The expression of cy ... Full text Link to item Cite

High-throughput identification and dendritic cell-based functional validation of MHC class I-restricted Mycobacterium tuberculosis epitopes.

Journal Article Sci Rep · April 23, 2014 Featured Publication Emergence of drug-resistant strains of the pathogen Mycobacterium tuberculosis (Mtb) and the ineffectiveness of BCG in curtailing Mtb infection makes vaccine development for tuberculosis an important objective. Identifying immunogenic CD8+ T cell peptide e ... Full text Link to item Cite

EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss.

Journal Article Clin Cancer Res · February 15, 2014 PURPOSE: Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed in both tumors and normal tissues have led to ... Full text Link to item Cite

Immunological targeting of cytomegalovirus for glioblastoma therapy.

Journal Article Oncoimmunology · 2014 Human cytomegalovirus (CMV) is purportedly present in glioblastoma (GBM) while absent from the normal brain, making CMV antigens potentially ideal immunological anti-GBM targets. We recently demonstrated that patient-derived CMV pp65-specific T cells are c ... Full text Link to item Cite

Programming human dendritic cells with mRNA

Journal Article Methods in Molecular Biology · December 1, 2013 Featured Publication Transfecting with in vitro transcribed, protein-encoding mRNA is a simple yet effective method to express high levels of the desired RNA-encoded proteins in primary cells. Cells can be transfected with antigenencoding mRNA, which is translated into protein ... Full text Cite

Local secretion of IL-12 augments the therapeutic impact of dendritic cell-tumor cell fusion vaccination.

Journal Article J Surg Res · December 2013 BACKGROUND: The development of dendritic cell (DC)-tumor fusion vaccines is a promising approach in cancer immunotherapy. Using fusion vaccines allows a broad spectrum of known and unidentified tumor-associated antigens to be presented in the context of MH ... Full text Link to item Cite

Melanoma immunotherapy using mature DCs expressing the constitutive proteasome.

Journal Article J Clin Invest · July 2013 BACKGROUND: Many cancers, including melanoma, exclusively express constitutive proteasomes (cPs) and are unable to express immunoproteasomes (iPs). In contrast, mature DCs used for immunotherapy exclusively express iPs. Since proteasomes generate peptides ... Full text Link to item Cite

Impact of anti-CD25 monoclonal antibody on dendritic cell-tumor fusion vaccine efficacy in a murine melanoma model.

Journal Article J Transl Med · June 17, 2013 BACKGROUND: A promising cancer vaccine involves the fusion of tumor cells with dendritic cells (DCs). As such, a broad spectrum of both known and unidentified tumor antigens is presented to the immune system in the context of the potent immunostimulatory c ... Full text Link to item Cite

Transfection efficiency and transgene expression kinetics of mRNA delivered in naked and nanoparticle format.

Journal Article J Control Release · March 28, 2013 Featured Publication Transfection efficiencies and transgene expression kinetics of messenger RNA (mRNA), an emerging class of nucleic acid-based therapeutics, have been poorly characterized. In this study, we evaluated transfection efficiencies of mRNA delivered in naked and ... Full text Link to item Cite

Identification and characterization of an agonistic aptamer against the T cell costimulatory receptor, OX40.

Journal Article Nucleic Acid Ther · February 2013 Featured Publication Induction of an effective immune response that can target and eliminate malignant cells or virus-infected cells requires the stimulation of antigen-specific effector T cells. A productive and long-lasting memory response requires 2 signals: a specific sign ... Full text Link to item Cite

Immunologic targeting of FOXP3 in inflammatory breast cancer cells.

Journal Article PLoS One · 2013 Featured Publication The forkhead transcription factor FOXP3 is necessary for induction of regulatory T lymphocytes (Tregs) and their immunosuppressive function. We have previously demonstrated that targeting Tregs by vaccination of mice with murine FOXP3 mRNA-transfected dend ... Full text Link to item Cite

Programming human dendritic cells with mRNA.

Journal Article Methods Mol Biol · 2013 Featured Publication Transfecting with in vitro transcribed, protein-encoding mRNA is a simple yet effective method to express high levels of the desired RNA-encoded proteins in primary cells. Cells can be transfected with antigen-encoding mRNA, which is translated into protei ... Full text Link to item Cite

Engineering B cells with mRNA.

Journal Article Methods Mol Biol · 2013 Ex vivo activated B cells are an alternative source of antigen presenting cells (APC). However, the ability of ex vivo activated B cells to function as potent APCs has been a concern especially when compared to dendritic cells (DC). Herein, we introduce a ... Full text Link to item Cite

Isolation and generation of human dendritic cells.

Journal Article Curr Protoc Immunol · November 2012 Featured Publication Dendritic cells are highly specialized antigen-presenting cells (APC), which may be isolated or generated from human blood mononuclear cells. Although mature blood dendritic cells normally represent ∼0.2% of human blood mononuclear cells, their frequency c ... Full text Link to item Cite

A pilot study of IL-2Rα blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma.

Journal Article PLoS One · 2012 BACKGROUND: Preclinical studies in mice have demonstrated that the prophylactic depletion of immunosuppressive regulatory T-cells (T(Regs)) through targeting the high affinity interleukin-2 (IL-2) receptor (IL-2Rα/CD25) can enhance anti-tumor immunotherapy ... Full text Open Access Link to item Cite

Enhancement of anti-tumor immunity through local modulation of CTLA-4 and GITR by dendritic cells.

Journal Article Eur J Immunol · December 2011 Featured Publication Cancer vaccines have now demonstrated clinical efficacy, but immune modulatory mechanisms that prevent autoimmunity limit their effectiveness. Systemic administration of mAbs targeting the immune modulatory receptors CTLA-4 and glucocorticoid-induced TNFR- ... Full text Link to item Cite

RNA as performance-enhancers for dendritic cells.

Journal Article Expert Opin Biol Ther · April 2010 IMPORTANCE OF THE FIELD: Although studies have demonstrated that antigen-loaded dendritic cells (DC) elicit antigen-specific immune responses, the clinical benefit from DC-based cancer immunotherapy remains low. RNA, in the form of mRNA, has not only been ... Full text Link to item Cite

Dendritic cells engineered to secrete anti-GITR antibodies are effective adjuvants to dendritic cell-based immunotherapy.

Journal Article Cancer Gene Ther · December 2009 Featured Publication A number of monoclonal antibodies (mAbs) have been studied for their ability to enhance immune responses. Although these antibodies are effective in pre-clinical and clinical studies, they are costly and have occasionally been associated with adverse effec ... Full text Link to item Cite

Activated B cells modified by electroporation of multiple mRNAs encoding immune stimulatory molecules are comparable to mature dendritic cells in inducing in vitro antigen-specific T-cell responses.

Journal Article Immunology · October 2008 Featured Publication Ex-vivo-activated B cells are an alternative source of antigen-presenting cells (APCs) and a potential replacement for dendritic cells (DCs) in immunotherapy. However, the ability of ex-vivo-activated B cells to function as potent APCs has been a concern, ... Full text Link to item Cite

Assembling OX40 aptamers on a molecular scaffold to create a receptor-activating aptamer.

Journal Article Chem Biol · July 21, 2008 Featured Publication We show that a molecular scaffold can be utilized to convert a receptor binding aptamer into a receptor agonist. Many receptors (including tumor necrosis receptor family members) are activated when they are multimerized on the cell surface. Molecular scaff ... Full text Link to item Cite

Aptamers in immunotherapy.

Journal Article Hum Gene Ther · May 2008 Full text Link to item Cite

Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity.

Journal Article Cancer Res · January 1, 2007 Featured Publication Depletion of CD4+CD25+ regulatory T cells (Treg) by treatment with alphaCD25 antibody synergizes with vaccination protocols to engender protective immunity in mice. The effectiveness of targeting CD25 to eliminate Treg is limited by the fact that CD25, the ... Full text Link to item Cite

Systemic anti-CD25 monoclonal antibody administration safely enhances immunity in murine glioma without eliminating regulatory T cells.

Journal Article Clin Cancer Res · July 15, 2006 PURPOSE: Elevated proportions of regulatory T cells (T(reg)) are present in patients with a variety of cancers, including malignant glioma, yet recapitulative murine models are wanting. We therefore examined T(regs) in mice bearing malignant glioma and eva ... Full text Link to item Cite

Vaccination with mRNAs encoding tumor-associated antigens and granulocyte-macrophage colony-stimulating factor efficiently primes CTL responses, but is insufficient to overcome tolerance to a model tumor/self antigen.

Journal Article Cancer Immunol Immunother · June 2006 Featured Publication Immunization of mice with dendritic cells transfected ex vivo with tumor-associated antigen (TAA)-encoding mRNA primes cytotoxic T lymphocytes (CTL) that mediate tumor rejection. Here we investigated whether direct injection of TAA mRNA, encapsulated in ca ... Full text Link to item Cite

Tumor immunotherapy targeting fibroblast activation protein, a product expressed in tumor-associated fibroblasts.

Journal Article Cancer Res · December 1, 2005 Featured Publication Murine studies have shown that immunologic targeting of the tumor vasculature, a key element of the tumor stroma, can lead to protective immunity in the absence of significant pathology. In the current study, we expand the scope of stroma-targeted immunoth ... Full text Link to item Cite

Induction of CD4(+) and CD8(+) T-cell responses to the human stromal antigen, fibroblast activation protein: implication for cancer immunotherapy.

Journal Article Clin Cancer Res · August 1, 2005 PURPOSE: The propensity of tumor cells to escape immune elimination could limit, if not defeat, the long-term benefits of effective immunotherapeutic protocols. Immunologic targeting of tumor stroma could significantly reduce the ability of tumors to evade ... Full text Link to item Cite

Enhancing the immunostimulatory function of dendritic cells by transfection with mRNA encoding OX40 ligand.

Journal Article Blood · April 15, 2005 Featured Publication The objective of this study was to investigate whether the immunostimulatory properties of human monocyte-derived dendritic cells (DCs) could be enhanced by triggering OX40/OX40L signaling. Since monocyte-derived DCs possess only low-cell surface levels of ... Full text Link to item Cite

Induction of human dendritic cell maturation using transfection with RNA encoding a dominant positive toll-like receptor 4.

Journal Article J Immunol · June 1, 2004 Maturation of dendritic cells (DC) is critical for the induction of Ag-specific immunity. Ag-loaded DC matured with LPS, which mediates its effects by binding to Toll-like receptor 4 (TLR4), induce Ag-specific CTL in vitro and in vivo in animal models. How ... Full text Link to item Cite

Transfection of RNA encoding tumor antigens following maturation of dendritic cells leads to prolonged presentation of antigen and the generation of high-affinity tumor-reactive cytotoxic T lymphocytes.

Journal Article Mol Ther · May 2004 Common tumor vaccination strategies utilizing peptide-pulsed dendritic cells (DC) are limited to targeting antigens with known epitopes in patients expressing a defined restricting allele and can result in the preferential induction of low-avidity T cells ... Full text Link to item Cite

Inhibition of invariant chain expression in dendritic cells presenting endogenous antigens stimulates CD4+ T-cell responses and tumor immunity.

Journal Article Blood · December 1, 2003 Induction of potent and sustained antiviral or antitumor immunity is dependent on the efficient activation of CD8+ and CD4+ T cells. While dendritic cells constitute a powerful platform for stimulating cellular immunity, presentation of endogenous antigens ... Full text Link to item Cite

Injection of immature dendritic cells into adjuvant-treated skin obviates the need for ex vivo maturation.

Journal Article J Immunol · December 1, 2003 Featured Publication A key and limiting step in the process of generating human monocyte-derived dendritic cells (DC) for clinical applications is maturation. In the setting of immunotherapy, DC are matured ex vivo by culturing them with various agents that mimic the condition ... Full text Link to item Cite

Multivalent RNA aptamers that inhibit CTLA-4 and enhance tumor immunity.

Journal Article Cancer Res · November 1, 2003 Featured Publication The potency of cancer immunotherapy can be enhanced by administration of high-avidity ligands specific to receptors expressed on T cells. Antibodies or cytokines are the main agents used in such capacity. Antibody-mediated inhibition of cytotoxic T cell an ... Link to item Cite

Synergy between tumor immunotherapy and antiangiogenic therapy.

Journal Article Blood · August 1, 2003 Featured Publication This study tested the hypothesis that combination of antiangiogenic therapy and tumor immunotherapy of cancer is synergistic. To inhibit angiogenesis, mice were immunized with dendritic cells (DCs) transfected with mRNA that encode products that are prefer ... Full text Link to item Cite

Immunotherapy with autologous, human dendritic cells transfected with carcinoembryonic antigen mRNA.

Journal Article Cancer Invest · June 2003 Immunizations with dendritic cells (DC) transfected with RNA encoding tumor antigens induce potent tumor antigen-specific immune responses in vitro and in murine models. We performed a phase I study of patients with advanced carcinoembryonic antigen (CEA)- ... Full text Link to item Cite

RNA-transfected dendritic cells.

Journal Article Expert Rev Vaccines · December 2002 Based on their unique ability to stimulate primary immune responses, dendritic cells are the most potent antigen-presenting cells known. This ability stems from the fact that they are very efficient at the uptake and processing of antigen and they express ... Full text Link to item Cite

Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells.

Journal Article Ann Surg · April 2002 Featured Publication OBJECTIVE: To demonstrate the feasibility of inducing tumor antigen-specific immune responses in patients with metastatic cancer using total tumor RNA-loaded dendritic cells (DCs). SUMMARY BACKGROUND DATA: The authors have shown that DCs transfected with m ... Full text Link to item Cite

Influence of CD4 T cells and the source of major histocompatibility complex class II-restricted peptides on cytotoxic T-cell priming by dendritic cells.

Journal Article Immunology · January 2002 Featured Publication We have previously reported that bone marrow derived dendritic cells (DC) pulsed with major histocompatibility complex (MHC) class I-restricted peptide efficiently prime a cytotoxic T lymphocyte (CTL) response in vivo. Here we assess the involvement of CD4 ... Full text Link to item Cite

The feasibility and safety of immunotherapy with dendritic cells loaded with CEA mRNA following neoadjuvant chemoradiotherapy and resection of pancreatic cancer.

Journal Article Int J Gastrointest Cancer · 2002 BACKGROUND: Resected pancreatic cancer has a high risk of recurrence and mortality despite the the use of chemoradiotherapy. Because pancreatic cancers express tumor antigens such as carcinoembryonic antigen (CEA), it may be possible to immunize patients t ... Full text Link to item Cite

Induction of polyclonal prostate cancer-specific CTL using dendritic cells transfected with amplified tumor RNA.

Journal Article J Immunol · March 1, 2001 Polyvalent cancer vaccines targeting the entire antigenic spectrum on tumor cells may represent a superior therapeutic strategy for cancer patients than vaccines solely directed against single Ags. In this study, we show that autologous dendritic cells (DC ... Full text Link to item Cite

Preoperative mobilization of circulating dendritic cells by Flt3 ligand administration to patients with metastatic colon cancer.

Journal Article J Clin Oncol · December 1, 2000 Featured Publication PURPOSE: To evaluate preoperative dendritic cell (DC) mobilization and tumor infiltration after administration of Flt3 ligand (Flt3L) to patients with metastatic colon cancer. PATIENTS AND METHODS: Twelve patients with colon cancer metastatic to the liver ... Full text Link to item Cite

A subset of human monocyte-derived dendritic cells expresses high levels of interleukin-12 in response to combined CD40 ligand and interferon-gamma treatment.

Journal Article Blood · November 15, 2000 Dendritic cells (DCs) may arise from multiple lineages and progress through a series of intermediate stages until fully mature, at which time they are capable of optimal antigen presentation and T-cell activation. High cell surface expression of CD83 is pr ... Link to item Cite

Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells.

Journal Article Nat Med · September 2000 Featured Publication The polypeptide component of telomerase (TERT) is an attractive candidate for a broadly expressed tumor rejection antigen because telomerase is silent in normal tissues but is reactivated in more than 85% of cancers. Here we show that immunization against ... Full text Link to item Cite

Phenotypic and functional maturation of dendritic cells mediated by heparan sulfate.

Journal Article J Immunol · August 1, 2000 Primary immune responses are thought to be induced by dendritic cells. To promote such responses, dendritic cells must be activated by exogenous agonists, such as LPS, or by products of activated leukocytes, such as TNF-alpha and IL-1. How dendritic cells ... Full text Link to item Cite

Involvement of an ATP-dependent peptide chaperone in cross-presentation after DNA immunization.

Journal Article J Immunol · July 15, 2000 Immunization with plasmid DNA holds promise as a vaccination strategy perhaps useful in situations that currently lack vaccines, since the major means of immune induction may differ from more conventional approach. In the present study, we demonstrate that ... Full text Link to item Cite

Effectiveness of combined interleukin 2 and B7.1 vaccination strategy is dependent on the sequence and order: a liposome-mediated gene therapy treatment for bladder cancer.

Journal Article Clin Cancer Res · July 2000 We have developed a novel liposome-mediated immunogene therapy using interleukin 2 (IL-2) and B7.1 in a murine bladder cancer model. A carcinogen-induced murine bladder cancer cell line, MBT-2, was transfected with cationic liposome 1,2-dimyristyloxypropyl ... Link to item Cite

Human dendritic cells transfected with RNA encoding prostate-specific antigen stimulate prostate-specific CTL responses in vitro.

Journal Article J Immunol · May 15, 2000 Although immunological tolerance to self Ags represents an important mechanism to prevent normal tissue injury, there is growing evidence that tolerance to tumor Ags, which often represent normal peripherally expressed proteins, is not absolute and can be ... Full text Link to item Cite

RNA transfected dendritic cells as cancer vaccines.

Journal Article Curr Opin Mol Ther · April 2000 Immunization with dendritic cells loaded with tumor antigens could represent a powerful method of inducing antitumor immunity. Studies from several laboratories have shown that immunization with dendritic cells pulsed with specific antigens prime cytotoxic ... Link to item Cite

Induction of tumor immunity and cytotoxic T lymphocyte responses using dendritic cells transfected with messenger RNA amplified from tumor cells.

Journal Article Cancer Res · February 15, 2000 Featured Publication Unique patient-specific tumor antigens may constitute the dominant antigens in the antitumor immune response. Hence, vaccination with the patient's own repertoire of tumor antigens may offer a superior strategy to elicit protective immunity. We have shown ... Link to item Cite

Induction of cytotoxic T lymphocytes with dendritic cells transfected with human papillomavirus E6 and E7 RNA: implications for cervical cancer immunotherapy.

Journal Article J Immunother · 2000 Featured Publication Human papillomavirus (HPV) infection is associated with cervical cancer. The high-risk HPV E6 and E7 oncoproteins are constitutively expressed in most cervical carcinoma cells, and are, therefore, attractive antigens for cytotoxic T-lymphocyte (CTL)-mediat ... Full text Link to item Cite

Induction of carcinoembryonic antigen (CEA)-specific cytotoxic T-lymphocyte responses in vitro using autologous dendritic cells loaded with CEA peptide or CEA RNA in patients with metastatic malignancies expressing CEA.

Journal Article Int J Cancer · July 2, 1999 The application of dendritic cells (DC) to the active immunotherapy of cancer currently relies on the generation of potent DC capable of presenting tumor antigens such as carcinoembryonic antigen (CEA). It is unknown whether the T cells of patients with ad ... Full text Link to item Cite

A Phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen.

Journal Article Clin Cancer Res · June 1999 Dendritic cells (DCs), antigen-presenting cells capable of priming naive T cells to specific antigens in an HLA-restricted fashion, have been demonstrated to induce protective T cell-mediated immunity in tumor-bearing animals. We performed this study to te ... Link to item Cite

Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides.

Journal Article J Immunol · June 1, 1999 Calreticulin is an endoplasmic reticulum (ER) chaperone that displays lectin activity and contributes to the folding pathways for nascent glycoproteins. Calreticulin also participates in the reactions yielding assembly of peptides onto nascent MHC class I ... Link to item Cite

Optimization of the sequence of antigen loading and CD40-ligand-induced maturation of dendritic cells.

Journal Article Cancer Res · July 15, 1998 Featured Publication Dendritic cells (DCs), matured by CD40-ligand (CD40L), undergo marked changes in their ability to process and present antigen, resulting in augmented lymphocyte stimulatory activity. We demonstrate that the form of the tumor antigen (peptide or genetic mat ... Link to item Cite

Dendritic cell/macrophage precursors capture exogenous antigen for MHC class I presentation by dendritic cells.

Journal Article Eur J Immunol · June 1998 Featured Publication Presentation of MHC class I antigens by professional antigen-presenting cells (APC) is an important pathway in priming cytotoxic T lymphocyte responses in vivo. This study sought to identify the nature of the professional APC responsible for indirect class ... Full text Link to item Cite

Immunotherapy of cancer with dendritic-cell-based vaccines.

Journal Article Cancer Immunol Immunother · April 1998 Animal studies have shown that vaccination with genetically modified tumor cells or with dendritic cells (DC) pulsed with tumor antigens are potent strategies to elicit protective immunity in tumor-bearing animals, more potent than "conventional" strategie ... Full text Link to item Cite

Induction of primary carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocytes in vitro using human dendritic cells transfected with RNA.

Journal Article Nat Biotechnol · April 1998 Featured Publication Dendritic cells (DC) generated from the peripheral blood mononuclear cells of healthy individuals or from cancer patients transfected with carcinoembryonic antigen (CEA) mRNA stimulate a potent CD8+ cytotoxic T lymphocyte (CTL) response in vitro. DCs are e ... Full text Link to item Cite

Induction of primary, human antigen-specific cytotoxic T lymphocytes in vitro using dendritic cells pulsed with peptides.

Journal Article J Immunother · January 1998 Featured Publication Using a murine metastasis model, we have previously shown that antigen-presenting cells (APC) loaded with unfractionated peptides derived from poorly immunogenic, highly metastatic tumor cells represent a potent form of tumor vaccine. The antimetastatic ef ... Full text Link to item Cite

Heparan sulfate modulate allogeneic T cell responses stimulated by dendritic cells

Conference FASEB Journal · 1998 Heparan sulfate (HS) is a biologically active glycosaminoglycan which is released from cell surfaces or extracellular matrices under the circumstances of tissue injury or inflammation. We have reported previously that HS modulates T cell immune responses b ... Cite

DNA vaccines and immunity to herpes simplex virus.

Journal Article Curr Top Microbiol Immunol · 1998 Full text Link to item Cite

Cancer immunotherapy with tumor RNA transfected dendritic cell vaccines.

Conference JOURNAL OF LEUKOCYTE BIOLOGY · January 1, 1998 Link to item Cite

Bone marrow-generated dendritic cells pulsed with tumor extracts or tumor RNA induce antitumor immunity against central nervous system tumors.

Journal Article J Exp Med · October 6, 1997 Recent studies have shown that the brain is not a barrier to successful active immunotherapy that uses gene-modified autologous tumor cell vaccines. In this study, we compared the efficacy of two types of vaccines for the treatment of tumors within the cen ... Full text Link to item Cite

Immunotherapy of cancer with dendritic cell-based tumor vaccines

Conference CANCER GENE THERAPY · September 1, 1997 Link to item Cite

Regression of tumors in mice vaccinated with professional antigen-presenting cells pulsed with tumor extracts.

Journal Article Int J Cancer · March 17, 1997 Vaccination with tumor extracts circumvents the need to identify specific tumor rejection antigens and extends the use of active immunotherapy to the vast majority of cancers, in which specific tumor antigens have not yet been identified. In this study we ... Full text Link to item Cite

Antigen-presenting cells pulsed with unfractionated tumor-derived peptides are potent tumor vaccines.

Journal Article Eur J Immunol · March 1997 Vaccination with peptides isolated from tumor cells circumvents the need for identifying specific tumor rejection antigens and extends the use of active immunotherapy to the majority of cancers where specific tumor antigens have not yet been identified. In ... Full text Link to item Cite

Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo.

Journal Article J Exp Med · August 1, 1996 Featured Publication Immunization with defined tumor antigens is currently limited to a small number of cancers where candidates for tumor rejection antigens have been identified. In this study we investigated whether pulsing dendritic cells (DC) with tumor-derived RNA is an e ... Full text Link to item Cite

Cells treated with TAP-2 antisense oligonucleotides are potent antigen-presenting cells in vitro and in vivo.

Journal Article J Immunol · March 1, 1996 Treatment of RMA and EL4 cells or freshly isolated splenocytes with antisense (AS) oligonucleotides directed against the TAP-2 gene recreates the phenotype seen in cells that are genetically deficient in TAP function. Cells incubated with AS oligonucleotid ... Link to item Cite

Priming for virus-specific CD8+ but not CD4+ cytotoxic T lymphocytes with synthetic lipopeptide is influenced by acylation units and liposome encapsulation.

Journal Article Vaccine · December 1995 Synthetic peptides of the herpes simplex virus glycoprotein B synthesized either as a free form or derivatized with one (PAM1) or three palmitic acids (PAM3Cys) were used to assess the in vivo priming efficacy of high affinity virus-specific CTL induction. ... Full text Link to item Cite

Role of macrophages and dendritic cells in primary cytotoxic T lymphocyte responses.

Journal Article Int Immunol · April 1995 Featured Publication The successful induction of class I restricted cytotoxic T lymphocytes (CTL) responses with soluble non-replicating antigens relies upon vehicles which deliver antigen in vivo appropriately to antigen presenting cells (APC), which for CTL may be dendritic ... Full text Link to item Cite

Expression of cytokine mRNA in murine splenic dendritic cells and better induction of T cell-derived cytokines by dendritic cells than by macrophages during in vitro costimulation assay using specific antigens.

Journal Article J Leukoc Biol · February 1995 Among antigen-presenting cells dendritic cells (DC) have the unique ability to generate primary T cell response. The reasons for the superior inductive property of DC still remain obscure. The explanations offered include higher expression of CD80, MHCII, ... Full text Link to item Cite

Induction in vitro of primary cytotoxic T-lymphocyte responses with DNA encoding herpes simplex virus proteins.

Journal Article J Virol · September 1994 Vaccines which successfully protect against virus infections usually need to induce a broadly reactive immune response which includes the induction of cytotoxic T lymphocytes (CTL). In this study, we have used a convenient in vitro approach to investigate ... Full text Link to item Cite

Vaccination with the immediate-early protein ICP47 of herpes simplex virus-type 1 (HSV-1) induces virus-specific lymphoproliferation, but fails to protect against lethal challenge.

Journal Article Virology · April 1994 Assessing the immunobiological function of the individual proteins of herpes simplex virus-type 1 (HSV-1) continues to be important in elucidating virus-host interactions and for the rational design of subunit vaccines. In this report, the non-structural, ... Full text Link to item Cite

Cholera toxin acts as a potent adjuvant for the induction of cytotoxic T-lymphocyte responses with non-replicating antigens.

Journal Article Immunology · March 1994 Cholera toxin (CT) is a strong systemic and mucosal adjuvant that greatly enhances IgG and IgA immune responses, but its adjuvant effects for cellular immunity, particularly class I-restricted cytotoxic T lymphocyte (CTL) responses, are less well understoo ... Link to item Cite

Induction of primary, antiviral cytotoxic, and proliferative responses with antigens administered via dendritic cells.

Journal Article J Virol · July 1993 Featured Publication Cytotoxic T lymphocytes (CTL) play an essential role in recovery from viral infections, but induction of CTL responses with nonreplicating antigens is difficult to achieve. Exogenous antigens, such as viral proteins and peptides, normally induce CD4+ T-cel ... Full text Link to item Cite

Recognition by and in vitro induction of cytotoxic T lymphocytes against predicted epitopes of the immediate-early protein ICP27 of herpes simplex virus.

Journal Article J Virol · January 1993 The identification of herpes simplex virus type 1 (HSV-1) proteins and the minimal epitopes within these proteins which serve as targets for cytotoxic T lymphocytes (CTL) remains an important goal for the development of effective vaccine strategies. In thi ... Full text Link to item Cite

Class I restricted CTL recognition of a soluble protein delivered by liposomes containing lipophilic polylysines.

Journal Article J Immunol Methods · August 10, 1992 CD8+ cytotoxic lymphocytes recognize peptides derived from endogenous antigens complexed with class I major histocompatibility complex while CD4+ helper cells recognize peptides from exogenous antigens bound to class II MHC molecules. A soluble protein can ... Full text Link to item Cite

Liposomes as antigen delivery systems in viral immunity.

Journal Article Semin Immunol · April 1992 Since their first description, liposomes have been put to a wide variety of uses. Encapsulation or incorporation of antigens into liposomes markedly enhances the immunogenicity of the antigen. The type of immune response elicited by the liposome is found t ... Link to item Cite

In vivo cytotoxic T lymphocyte induction with soluble proteins administered in liposomes.

Journal Article J Immunol · March 1, 1992 The in vivo induction of a CTL response usually requires that Ag be endogenously synthesized so that appropriate processing can occur. In most of the few examples where successful CTL induction was reported with proteins and peptides, unacceptable adjuvant ... Link to item Cite

Soluble proteins delivered to dendritic cells via pH-sensitive liposomes induce primary cytotoxic T lymphocyte responses in vitro.

Journal Article J Exp Med · February 1, 1992 Featured Publication Effective immunity to many infectious agents, particularly viruses, requires a CD8+ cytotoxic T lymphocyte (CTL) response. Understanding how to achieve CTL induction with soluble proteins is important for vaccine development since such antigens are usually ... Full text Link to item Cite