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Amy Claudine Hobeika

Assistant Professor in Surgery
Surgery, Surgical Sciences
Box 2606 Med Ctr, Durham, NC 27710
404A MSRB 1, Research Dr, Durham, NC 27710

Selected Publications


Clinical trials of self-replicating RNA-based cancer vaccines.

Journal Article Cancer gene therapy · June 2023 Therapeutic cancer vaccines, designed to activate immune effectors against tumor antigens, utilize a number of different platforms for antigen delivery. Among these are messenger RNAs (mRNA), successfully deployed in some prophylactic SARS-CoV2 vaccines. T ... Full text Cite

Combination of a novel heat shock protein 90-targeted photodynamic therapy with PD-1/PD-L1 blockade induces potent systemic antitumor efficacy and abscopal effect against breast cancers.

Journal Article J Immunother Cancer · September 2022 BACKGROUND: We previously demonstrated potent antitumor activity against human breast cancer xenografts using photodynamic therapy (PDT) targeting a novel tumor-specific photosensitizer (HS201), which binds heat shock protein 90 (HS201-PDT). However, induc ... Full text Link to item Cite

Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma.

Journal Article Nat Commun · June 13, 2022 Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from n ... Full text Link to item Cite

HSP90-Specific nIR Probe Identifies Aggressive Prostate Cancers: Translation from Preclinical Models to a Human Phase I Study.

Journal Article Mol Cancer Ther · January 2022 A noninvasive test to discriminate indolent prostate cancers from lethal ones would focus treatment where necessary while reducing overtreatment. We exploited the known activity of heat shock protein 90 (Hsp90) as a chaperone critical for the function of n ... Full text Link to item Cite

Changes in Peripheral Blood Regulatory T Cells and IL-6 and IL-10 Levels Predict Response of Pediatric Medulloblastoma and Germ Cell Tumors With Residual or Disseminated Disease to Craniospinal Irradiation.

Journal Article Int J Radiat Oncol Biol Phys · October 1, 2021 PURPOSE: Radiation therapy (RT) modulates immune cells and cytokines, resulting in both clinically beneficial and detrimental effects. The changes in peripheral blood T lymphocyte subsets and cytokines during RT for pediatric brain tumors and the associati ... Full text Link to item Cite

Blood microbiota diversity determines response of advanced colorectal cancer to chemotherapy combined with adoptive T cell immunotherapy.

Journal Article Oncoimmunology · 2021 Human microbiota influence the response of malignancies to treatment with immune checkpoint blockade; however, their impact on other forms of immunotherapy is poorly understood. This study explored the effect of blood microbiota on clinical efficacy, repre ... Full text Link to item Cite

Long-term survival of patients with stage III colon cancer treated with VRP-CEA(6D), an alphavirus vector that increases the CD8+ effector memory T cell to Treg ratio.

Journal Article J Immunother Cancer · November 2020 BACKGROUND: There remains a significant need to eliminate the risk of recurrence of resected cancers. Cancer vaccines are well tolerated and activate tumor-specific immune effectors and lead to long-term survival in some patients. We hypothesized that vacc ... Full text Link to item Cite

Adoptive immunotherapy with autologous T-cell infusions reduces opioid requirements in advanced cancer patients.

Journal Article Pain · January 2020 Relief of cancer-related pain remains challenging despite the availability of a range of opioid and nonopioid medications. Animal models demonstrate that T lymphocytes may mediate analgesia by producing endogenous opioids, but definitive clinical data are ... Full text Link to item Cite

Clinical efficacy of intra-cavitary infusions of autologous dendritic cell/cytokine-induced killer cell products for the treatment of refractory malignant pleural effusions and ascites.

Journal Article Am J Transl Res · 2020 To explore the safety and efficacy of intra-cavitary infusions of autologous mixed dendritic cell (DC)-cytokine-induced killer (CIK) cell products in advanced cancer patients with malignant pleural effusions or ascites. DC-CIKs were expanded ex vivo (mean ... Link to item Cite

Predictive significance of T cell subset changes during ex vivo generation of adoptive cellular therapy products for the treatment of advanced non-small cell lung cancer.

Journal Article Oncol Lett · December 2019 Adoptive T cell immunotherapy with cytokine-induced killer cells (CIKs) has been demonstrated to prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate whether the expansion of effect ... Full text Open Access Link to item Cite

Immune correlates of clinical benefit in a phase I study of hyperthermia with adoptive T cell immunotherapy in patients with solid tumors.

Journal Article Int J Hyperthermia · November 2019 Purpose: To characterize the T cell receptor (TCR) repertoire, serum cytokine levels, peripheral blood T lymphocyte populations, safety, and clinical efficacy of hyperthermia (HT) combined with autologous adoptive cell therapy (ACT) and either salvage chem ... Full text Link to item Cite

Functional CD3+CD8+PD1- T Cell Accumulation and PD-L1 Expression Increases During Tumor Invasion in DCIS of the Breast.

Journal Article Clin Breast Cancer · October 2019 BACKGROUND: The changes in T cell subsets and programmed death ligand 1 (PD-L1) expression during the transition from ductal carcinoma in situ (DCIS) to early invasive breast cancer had not been well studied. PATIENTS AND METHODS: A total of 85 DCIS patien ... Full text Link to item Cite

Impact of synchronized anti-PD-1 with Ad-CEA vaccination on inhibition of colon cancer growth.

Journal Article Immunotherapy · August 2019 Aim: The purpose of this study was to determine whether addition of anti-PD-1 antibody increased the immunogenicity and anti-tumor activity of Ad-CEA vaccination in a murine model of colon cancer. Methods: Ad-CEA was administered prior to implantation of M ... Full text Link to item Cite

Combination of DC/CIK adoptive T cell immunotherapy with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients: a prospective patients' preference-based study (PPPS).

Journal Article Clin Transl Oncol · June 2019 BACKGROUND: Advanced non-small cell lung cancer (NSCLC) has remained challenging to treat effectively. This study aimed to investigate the clinical effects and safety of immunotherapy with dendritic cells and cytokine-induced killer cells (DC-CIK) administ ... Full text Link to item Cite

Vaccine-Induced Memory CD8+ T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study.

Journal Article Clin Cancer Res · May 1, 2019 PURPOSE: Immune-based therapy for metastatic breast cancer has had limited success, particularly in molecular subtypes with low somatic mutations rates. Strategies to augment T-cell infiltration of tumors include vaccines targeting established oncogenic dr ... Full text Open Access Link to item Cite

Prospective randomized comparative study on rivaroxaban and LMWH for prophylaxis of post-apheresis thrombosis in adoptive T cell immunotherapy cancer patients.

Journal Article J Thromb Thrombolysis · May 2019 Autologous adoptive T cell immunotherapy has been recognized as an effective treatment for cancer patients. The initial qualified lymphocytes is the core element determining the immunotherapeutic outcomes clinically. Cell separator based apheresis procedur ... Full text Link to item Cite

Autologous Dendritic Cell-Cytokine Induced Killer Cell Immunotherapy Combined with S-1 Plus Cisplatin in Patients with Advanced Gastric Cancer: A Prospective Study.

Journal Article Clin Cancer Res · March 1, 2019 PURPOSE: We have assessed the combination of DC-CIK with S-1 plus cisplatin chemotherapy in advanced gastric cancer (AGC) and the role of mutational analysis of circulating tumor DNA (ctDNA) and T-cell receptor (TCR) repertoire in predicting clinical outco ... Full text Link to item Cite

Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients

Conference Cancer Research · February 15, 2019 AbstractBackground: Immune-based therapy for metastatic breast cancer has had limited success. Strategies to augment adaptive immunity include vaccines targeting genomic amplifications like Human Epidermal G ... Full text Cite

Polyfunctional anti-human epidermal growth factor receptor 3 (anti-HER3) antibodies induced by HER3 vaccines have multiple mechanisms of antitumor activity against therapy resistant and triple negative breast cancers.

Journal Article Breast Cancer Res · August 9, 2018 BACKGROUND: Upregulation of human epidermal growth factor receptor 3 (HER3) is a major mechanism of acquired resistance to therapies targeting its heterodimerization partners epidermal growth factor receptor (EGFR) and human epidermal growth factor recepto ... Full text Link to item Cite

CYP1A1 genetic polymorphism is a promising predictor to improve chemotherapy effects in patients with metastatic breast cancer treated with docetaxel plus thiotepa vs. docetaxel plus capecitabine.

Journal Article Cancer Chemother Pharmacol · February 2018 PURPOSE: A prospective study was performed to compare the outcome for metastatic breast cancer (MBC) patients treated with docetaxel plus thiotepa (DT) or docetaxel plus capecitabine (DC), and to explore the value of CYP1A1*2C polymorphisms in predicting c ... Full text Link to item Cite

Clinical trials of self-replicating RNA-based cancer vaccines.

Journal Article Cancer gene therapy · June 2023 Therapeutic cancer vaccines, designed to activate immune effectors against tumor antigens, utilize a number of different platforms for antigen delivery. Among these are messenger RNAs (mRNA), successfully deployed in some prophylactic SARS-CoV2 vaccines. T ... Full text Cite

Combination of a novel heat shock protein 90-targeted photodynamic therapy with PD-1/PD-L1 blockade induces potent systemic antitumor efficacy and abscopal effect against breast cancers.

Journal Article J Immunother Cancer · September 2022 BACKGROUND: We previously demonstrated potent antitumor activity against human breast cancer xenografts using photodynamic therapy (PDT) targeting a novel tumor-specific photosensitizer (HS201), which binds heat shock protein 90 (HS201-PDT). However, induc ... Full text Link to item Cite

Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma.

Journal Article Nat Commun · June 13, 2022 Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from n ... Full text Link to item Cite

HSP90-Specific nIR Probe Identifies Aggressive Prostate Cancers: Translation from Preclinical Models to a Human Phase I Study.

Journal Article Mol Cancer Ther · January 2022 A noninvasive test to discriminate indolent prostate cancers from lethal ones would focus treatment where necessary while reducing overtreatment. We exploited the known activity of heat shock protein 90 (Hsp90) as a chaperone critical for the function of n ... Full text Link to item Cite

Changes in Peripheral Blood Regulatory T Cells and IL-6 and IL-10 Levels Predict Response of Pediatric Medulloblastoma and Germ Cell Tumors With Residual or Disseminated Disease to Craniospinal Irradiation.

Journal Article Int J Radiat Oncol Biol Phys · October 1, 2021 PURPOSE: Radiation therapy (RT) modulates immune cells and cytokines, resulting in both clinically beneficial and detrimental effects. The changes in peripheral blood T lymphocyte subsets and cytokines during RT for pediatric brain tumors and the associati ... Full text Link to item Cite

Blood microbiota diversity determines response of advanced colorectal cancer to chemotherapy combined with adoptive T cell immunotherapy.

Journal Article Oncoimmunology · 2021 Human microbiota influence the response of malignancies to treatment with immune checkpoint blockade; however, their impact on other forms of immunotherapy is poorly understood. This study explored the effect of blood microbiota on clinical efficacy, repre ... Full text Link to item Cite

Long-term survival of patients with stage III colon cancer treated with VRP-CEA(6D), an alphavirus vector that increases the CD8+ effector memory T cell to Treg ratio.

Journal Article J Immunother Cancer · November 2020 BACKGROUND: There remains a significant need to eliminate the risk of recurrence of resected cancers. Cancer vaccines are well tolerated and activate tumor-specific immune effectors and lead to long-term survival in some patients. We hypothesized that vacc ... Full text Link to item Cite

Adoptive immunotherapy with autologous T-cell infusions reduces opioid requirements in advanced cancer patients.

Journal Article Pain · January 2020 Relief of cancer-related pain remains challenging despite the availability of a range of opioid and nonopioid medications. Animal models demonstrate that T lymphocytes may mediate analgesia by producing endogenous opioids, but definitive clinical data are ... Full text Link to item Cite

Clinical efficacy of intra-cavitary infusions of autologous dendritic cell/cytokine-induced killer cell products for the treatment of refractory malignant pleural effusions and ascites.

Journal Article Am J Transl Res · 2020 To explore the safety and efficacy of intra-cavitary infusions of autologous mixed dendritic cell (DC)-cytokine-induced killer (CIK) cell products in advanced cancer patients with malignant pleural effusions or ascites. DC-CIKs were expanded ex vivo (mean ... Link to item Cite

Predictive significance of T cell subset changes during ex vivo generation of adoptive cellular therapy products for the treatment of advanced non-small cell lung cancer.

Journal Article Oncol Lett · December 2019 Adoptive T cell immunotherapy with cytokine-induced killer cells (CIKs) has been demonstrated to prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate whether the expansion of effect ... Full text Open Access Link to item Cite

Immune correlates of clinical benefit in a phase I study of hyperthermia with adoptive T cell immunotherapy in patients with solid tumors.

Journal Article Int J Hyperthermia · November 2019 Purpose: To characterize the T cell receptor (TCR) repertoire, serum cytokine levels, peripheral blood T lymphocyte populations, safety, and clinical efficacy of hyperthermia (HT) combined with autologous adoptive cell therapy (ACT) and either salvage chem ... Full text Link to item Cite

Functional CD3+CD8+PD1- T Cell Accumulation and PD-L1 Expression Increases During Tumor Invasion in DCIS of the Breast.

Journal Article Clin Breast Cancer · October 2019 BACKGROUND: The changes in T cell subsets and programmed death ligand 1 (PD-L1) expression during the transition from ductal carcinoma in situ (DCIS) to early invasive breast cancer had not been well studied. PATIENTS AND METHODS: A total of 85 DCIS patien ... Full text Link to item Cite

Impact of synchronized anti-PD-1 with Ad-CEA vaccination on inhibition of colon cancer growth.

Journal Article Immunotherapy · August 2019 Aim: The purpose of this study was to determine whether addition of anti-PD-1 antibody increased the immunogenicity and anti-tumor activity of Ad-CEA vaccination in a murine model of colon cancer. Methods: Ad-CEA was administered prior to implantation of M ... Full text Link to item Cite

Combination of DC/CIK adoptive T cell immunotherapy with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients: a prospective patients' preference-based study (PPPS).

Journal Article Clin Transl Oncol · June 2019 BACKGROUND: Advanced non-small cell lung cancer (NSCLC) has remained challenging to treat effectively. This study aimed to investigate the clinical effects and safety of immunotherapy with dendritic cells and cytokine-induced killer cells (DC-CIK) administ ... Full text Link to item Cite

Vaccine-Induced Memory CD8+ T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study.

Journal Article Clin Cancer Res · May 1, 2019 PURPOSE: Immune-based therapy for metastatic breast cancer has had limited success, particularly in molecular subtypes with low somatic mutations rates. Strategies to augment T-cell infiltration of tumors include vaccines targeting established oncogenic dr ... Full text Open Access Link to item Cite

Prospective randomized comparative study on rivaroxaban and LMWH for prophylaxis of post-apheresis thrombosis in adoptive T cell immunotherapy cancer patients.

Journal Article J Thromb Thrombolysis · May 2019 Autologous adoptive T cell immunotherapy has been recognized as an effective treatment for cancer patients. The initial qualified lymphocytes is the core element determining the immunotherapeutic outcomes clinically. Cell separator based apheresis procedur ... Full text Link to item Cite

Autologous Dendritic Cell-Cytokine Induced Killer Cell Immunotherapy Combined with S-1 Plus Cisplatin in Patients with Advanced Gastric Cancer: A Prospective Study.

Journal Article Clin Cancer Res · March 1, 2019 PURPOSE: We have assessed the combination of DC-CIK with S-1 plus cisplatin chemotherapy in advanced gastric cancer (AGC) and the role of mutational analysis of circulating tumor DNA (ctDNA) and T-cell receptor (TCR) repertoire in predicting clinical outco ... Full text Link to item Cite

Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients

Conference Cancer Research · February 15, 2019 AbstractBackground: Immune-based therapy for metastatic breast cancer has had limited success. Strategies to augment adaptive immunity include vaccines targeting genomic amplifications like Human Epidermal G ... Full text Cite

Polyfunctional anti-human epidermal growth factor receptor 3 (anti-HER3) antibodies induced by HER3 vaccines have multiple mechanisms of antitumor activity against therapy resistant and triple negative breast cancers.

Journal Article Breast Cancer Res · August 9, 2018 BACKGROUND: Upregulation of human epidermal growth factor receptor 3 (HER3) is a major mechanism of acquired resistance to therapies targeting its heterodimerization partners epidermal growth factor receptor (EGFR) and human epidermal growth factor recepto ... Full text Link to item Cite

CYP1A1 genetic polymorphism is a promising predictor to improve chemotherapy effects in patients with metastatic breast cancer treated with docetaxel plus thiotepa vs. docetaxel plus capecitabine.

Journal Article Cancer Chemother Pharmacol · February 2018 PURPOSE: A prospective study was performed to compare the outcome for metastatic breast cancer (MBC) patients treated with docetaxel plus thiotepa (DT) or docetaxel plus capecitabine (DC), and to explore the value of CYP1A1*2C polymorphisms in predicting c ... Full text Link to item Cite

Circulating CD8+CD28- suppressor T cells tied to poorer prognosis among metastatic breast cancer patients receiving adoptive T-cell therapy: A cohort study.

Journal Article Cytotherapy · January 2018 BACKGROUND AIMS: This study aimed to determine the prognostic value of circulating CD8+CD28- T lymphocytes among breast cancer patients treated with adoptive T-lymphocyte immunotherapy after chemotherapy. METHODS: Two hundred and thirty-two breast cancer p ... Full text Link to item Cite

In Vivo Detection of HSP90 Identifies Breast Cancers with Aggressive Behavior.

Journal Article Clin Cancer Res · December 15, 2017 Purpose: Hsp90, a chaperone to numerous molecular pathways in malignant cells, is elevated in aggressive breast cancers. We hypothesized that identifying breast cells with elevated Hsp90 activity in situ could result in early detection of aggressive breast ... Full text Link to item Cite

Dendritic Cell/Cytokine-Induced Killer Cell Immunotherapy Combined with S-1 in Patients with Advanced Pancreatic Cancer: A Prospective Study.

Journal Article Clin Cancer Res · September 1, 2017 Purpose: Advanced pancreatic cancer has remained challenging to treat effectively. This study aimed to investigate the clinical effects and safety of immunotherapy with dendritic cells and cytokine-induced killer cells (DC-CIK) administered with the chemot ... Full text Link to item Cite

Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy.

Journal Article Oncoimmunology · 2017 Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-i ... Full text Link to item Cite

Vaccination targeting human HER3 alters the phenotype of infiltrating T cells and responses to immune checkpoint inhibition.

Journal Article Oncoimmunology · 2017 Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicabil ... Full text Link to item Cite

The prognostic value of peripheral CD4+CD25+ T lymphocytes among early stage and triple negative breast cancer patients receiving dendritic cells-cytokine induced killer cells infusion.

Journal Article Oncotarget · December 1, 2015 OBJECTIVE: This study aimed to assess the prognostic value of CD4+CD25+ T lymphocyte in peripheral blood among breast cancer patients treated with adoptive T lymphocytes immunotherapy. METHODS: 217 patients participated in the follow-up study. CD4+CD25+ pr ... Full text Link to item Cite

Precision cancer immunotherapy: optimizing dendritic cell-based strategies to induce tumor antigen-specific T-cell responses against individual patient tumors.

Journal Article J Immunother · May 2015 Most dendritic cell (DC)-based vaccines have loaded the DC with defined antigens, but loading with autologos tumor-derived antigens would generate DCs that activate personalized tumor-specific T-cell responses. We hypothesized that DC matured with an optim ... Full text Link to item Cite

Biomarkers and correlative endpoints for immunotherapy trials.

Journal Article Am Soc Clin Oncol Educ Book · 2013 Immunotherapies for lung cancer are reaching phase III clinical trial, but the ultimate success likely will depend on developing biomarkers to guide development and choosing patient populations most likely to benefit. Because the immune response to cancer ... Full text Link to item Cite

Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects.

Journal Article Cancer Immunol Immunother · November 2012 We recently demonstrated that Venezuelan equine encephalitis virus-based replicon particle (VRPs) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP-expressing i ... Full text Link to item Cite

Polyclonal HER2-specific antibodies induced by vaccination mediate receptor internalization and degradation in tumor cells.

Journal Article Breast Cancer Res · June 7, 2012 INTRODUCTION: Sustained HER2 signaling at the cell surface is an oncogenic mechanism in a significant proportion of breast cancers. While clinically effective therapies targeting HER2 such as mAbs and tyrosine kinase inhibitors exist, tumors overexpressing ... Full text Link to item Cite

Novel recombinant alphaviral and adenoviral vectors for cancer immunotherapy.

Journal Article Semin Oncol · June 2012 Although cellular immunotherapy based on autolgous dendritic cells (DCs) targeting antigens expressed by metastatic cancer has demonstrated clinical efficacy, the logistical challenges in generating an individualized cell product create an imperative to de ... Full text Link to item Cite

Phase 1 clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibition [corrected].

Journal Article J Transl Med · February 10, 2012 BACKGROUND: Patients with HER2-overexpressing metastatic breast cancer, despite initially benefiting from the monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor lapatinib, will eventually have progressive disease. HER2-based vaccin ... Full text Link to item Cite

Depleting regulatory T cells with arginine-rich, cell-penetrating, peptide-conjugated morpholino oligomer targeting FOXP3 inhibits regulatory T-cell function.

Journal Article Cancer Gene Ther · January 2012 CD4+CD25+regulatory T cells (T(reg)) impair anti-tumor and anti-viral immunity. As there are higher T(reg) levels in cancer patients compared with healthy individuals, there is considerable interest in eliminating them or altering their function as part of ... Full text Link to item Cite

P1-13-03: Zoledronic Acid Induces an Immune Response in Breast Cancer Patients through Stimulation of Central Memory and Effector Memory gamma/delta T-Cells.

Journal Article Cancer Research · December 15, 2011 AbstractBackground Zoledronic acid (ZA) in combination with endocrine therapy (ET) and ovarian ablation (OA) reported a DFS advantage in premenopausal women with early stage breast cancer (EBC) in ABCSG-12. ... Full text Cite

Increasing vaccine potency through exosome antigen targeting.

Journal Article Vaccine · November 21, 2011 While many tumor associated antigens (TAAs) have been identified in human cancers, efforts to develop efficient TAA "cancer vaccines" using classical vaccine approaches have been largely ineffective. Recently, a process to specifically target proteins to e ... Full text Link to item Cite

Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients.

Journal Article Clin Cancer Res · July 15, 2011 PURPOSE: The use of tumor-derived proteins as cancer vaccines is complicated by tolerance to these self-antigens. Tolerance may be broken by immunization with activated, autologous, ex vivo generated and antigen-loaded, antigen-presenting cells (APC); howe ... Full text Link to item Cite

MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer.

Journal Article Clin Cancer Res · May 15, 2011 PURPOSE: The purpose of this study is to test whether peptide epitopes chosen from among those naturally processed and overpresented within MHC molecules by malignant, but not normal cells, when formulated into cancer vaccines, could activate antitumor T-c ... Full text Link to item Cite

Polyclonal immune responses to antigens associated with cancer signaling pathways and new strategies to enhance cancer vaccines.

Journal Article Immunol Res · April 2011 Aberrant signaling pathways are a hallmark of cancer. A variety of strategies for inhibiting signaling pathways have been developed, but monoclonal antibodies against receptor tyrosine kinases have been among the most successful. A challenge for these ther ... Full text Link to item Cite

ADAM metallopeptidase domain 17 (ADAM17) is naturally processed through major histocompatibility complex (MHC) class I molecules and is a potential immunotherapeutic target in breast, ovarian and prostate cancers.

Journal Article Clin Exp Immunol · March 2011 Selection of suitable antigens is critical for the development of cancer vaccines. Most desirable are over-expressed cell surface proteins that may serve as targets for both antibodies and T cells, thus maximizing a concerted immune response. Towards this ... Full text Link to item Cite

Depletion of human regulatory T cells.

Journal Article Methods Mol Biol · 2011 Regulatory T cells (Treg) have become increasingly relevant in the study of human disease including cancer. Treg cells have been shown to inhibit anti-tumor immune responses, and elevated Treg levels have been associated with certain types of cancer. Simil ... Full text Link to item Cite

An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer.

Journal Article J Clin Invest · September 2010 Therapeutic anticancer vaccines are designed to boost patients' immune responses to tumors. One approach is to use a viral vector to deliver antigen to in situ DCs, which then activate tumor-specific T cell and antibody responses. However, vector-specific ... Full text Open Access Link to item Cite

Synergism from combined immunologic and pharmacologic inhibition of HER2 in vivo.

Journal Article Int J Cancer · June 15, 2010 The monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor lapatinib improve the clinical outcome of patients with HER2-overexpressing breast cancer. However, the majority of metastatic cancers will eventually progress, suggesting the ... Full text Link to item Cite

An adenoviral vaccine encoding full-length inactivated human Her2 exhibits potent immunogenicty and enhanced therapeutic efficacy without oncogenicity.

Journal Article Clin Cancer Res · March 1, 2010 PURPOSE: Overexpression of the breast cancer oncogene HER2 correlates with poor survival. Current HER2-directed therapies confer limited clinical benefits and most patients experience progressive disease. Because refractory tumors remain strongly HER2+, va ... Full text Link to item Cite

Immunomodulatory gene therapy prevents antibody formation and lethal hypersensitivity reactions in murine pompe disease.

Journal Article Mol Ther · February 2010 Infantile Pompe disease progresses to a lethal cardiomyopathy in absence of effective treatment. Enzyme-replacement therapy (ERT) with recombinant human acid alpha-glucosidase (rhGAA) has been effective in most patients with Pompe disease, but efficacy was ... Full text Link to item Cite

Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitive to T-cell killing mediated by CEA/CD3-bispecific T-cell-engaging BiTE antibody.

Journal Article Br J Cancer · January 5, 2010 BACKGROUND: Novel technologies to redirect T-cell killing against cancer cells are emerging. We hypothesised that metastatic human colorectal cancer (CRC) previously treated with conventional chemotherapy would be sensitive to T-cell killing mediated by ca ... Full text Link to item Cite

Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines.

Journal Article Blood · August 1, 2008 CD4(+)CD25(high)FoxP3(+) regulatory T (Treg) cells limit antigen-specific immune responses and are a cause of suppressed anticancer immunity. In preclinical and clinical studies, we assessed the immune consequences of FoxP3(+) Treg-cell depletion in patien ... Full text Link to item Cite

Detailed analysis of cytomegalovirus (CMV)-specific T cells expanded for adoptive immunotherapy of CMV infection following allogeneic stem cell transplantation for malignant disease.

Journal Article Cytotherapy · 2008 BACKGROUND: Cytomegalovirus (CMV) infection and its treatment causes significant morbidity following allogeneic stem cell transplantation (SCT) for malignancies. We studied the phenotype, function and growth kinetics of CMV pp65 antigen (Ag)-specific T cel ... Full text Link to item Cite

Current immunotherapeutic strategies in colon cancer.

Journal Article Surg Oncol Clin N Am · October 2007 Because chemotherapy is standard in the treatment of colorectal cancer, it is important to demonstrate whether immunizations may be given to patients receiving systemic chemotherapy. Although some studies have demonstrated immune responses in patients with ... Full text Link to item Cite

Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2.

Journal Article J Transl Med · September 6, 2007 BACKGROUND: The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopathy. Additi ... Full text Link to item Cite

Dendritic cell vaccines.

Journal Article Front Biosci · May 1, 2007 Dendritic cells are antigen-presenting cells that have been shown to stimulate tumor antigen-specific T cell responses in preclinical studies. Consequently, there has been intense interest in developing dendritic cell based cancer vaccines. A variety of me ... Full text Link to item Cite

Vascular endothelial growth factor and immunosuppression in cancer: current knowledge and potential for new therapy.

Journal Article Expert Opin Biol Ther · April 2007 Two decades of research into the role of immunosuppression and angiogenesis in tumor biology have revealed multiple links between the two. Vascular endothelial growth factor, originally thought to be solely involved in vascular growth and permeability, has ... Full text Link to item Cite

Monitoring immunity to cancer vaccines

Other Enhancer - Biotherapy of Cancer · December 4, 2006 The potential use of vaccines to treat and prevent cancer has developed into an area of intense research. Great success has been achieved historically with vaccines against infectious agents, and observations such as a graft vs leukemia effect and spontane ... Cite

NK cell activation by dendritic cell vaccine: a mechanism of action for clinical activity.

Journal Article Cancer Immunol Immunother · September 2006 Recent reports revealed that dendritic cell (DC)-natural killer (NK) cell interaction plays an important role in tumor immunity, but few DC vaccine studies have attempted to evaluate the non-specific, yet potentially clinically relevant, NK response to imm ... Full text Link to item Cite

Intracellular Cytokine Assays

Chapter · December 1, 2005 This chapter provides an overview of intracellular cytokine assays. Intracellular cytokine assays are a relatively new method of identifying cytokine production by individual T cells and have the ability to correlate cytokine expression with cell surface p ... Full text Cite

Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules.

Journal Article Clin Cancer Res · April 15, 2005 PURPOSE: To determine the safety and immunologic and clinical efficacy of a dendritic cell vaccine modified to hyperexpress costimulatory molecules and tumor antigen. EXPERIMENTAL DESIGN: In this phase I study, we administered one or two cycles of four tri ... Full text Link to item Cite

A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer.

Journal Article J Transl Med · February 21, 2005 BACKGROUND: There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of a ... Full text Link to item Cite

Recent developments in therapeutic cancer vaccines.

Journal Article Nat Clin Pract Oncol · February 2005 Therapeutic cancer vaccines are being developed with the intention of treating existing tumors or preventing tumor recurrence. While the results of clinical trials, predominantly in the metastatic setting have been sobering, the central hypothesis of activ ... Full text Link to item Cite

Enumerating antigen-specific T-cell responses in peripheral blood: a comparison of peptide MHC Tetramer, ELISpot, and intracellular cytokine analysis.

Journal Article J Immunother · 2005 Detection of the circulating antigen-specific T-cell response to immunization is an important biologic end point in clinical trials of cancer vaccines. Typically employed assays are peptide MHC tetramer, ELISpot, and intracellular cytokine analysis. Althou ... Full text Link to item Cite

Intracellular Cytokine Assays

Chapter · December 30, 2004 This chapter provides an overview of intracellular cytokine assays. Intracellular cytokine assays are a relatively new method of identifying cytokine production by individual T cells and have the ability to correlate cytokine expression with cell surface p ... Full text Cite

Active immunotherapy with Flt3-ligand mobilized peripheral blood dendritic cells loaded with carcinoembryonic antigen peptide in patients with metastatic malignancies

Journal Article Journal of Applied Research · December 1, 2004 Background: Dendritic cells (DC) loaded with tumor antigens induce immune responses in some cancer patients. However, the most commonly used method for obtaining clinical grade DC requires in vitro generation over 7 days in media containing cytokine, incre ... Cite

Flt3-ligand as a vaccine adjuvant: Results in a study of Flt3-ligand plus tetanus toxoid immunization

Journal Article Journal of Applied Research · December 1, 2004 Dendritic cells (DC) efficiently process and present antigens to the effector arm of the immune system, thereby stimulating immunity against antigens of both foreign and self origin. Administration of Flt3-ligand (FL) has been reported to increase dendriti ... Cite

Regulatory and effector T cell subsets and dendritic cells in breast cancer.

Journal Article J Clin Oncol · July 15, 2004 9697 Background: Successful immune responses against breast cancer may depend on the balance between immune stimulation mediated through dendritic cells (DC) & cytolytic T cells, and immune inhibition mediated in part by CD4+CD25+ regulatory T cells (Treg) ... 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

HER2 dendritic cell vaccines.

Journal Article Clin Breast Cancer · February 2003 HER2/neu, a tumor antigen overexpressed by a third of breast cancers, is a potential target for vaccine therapies. A particularly potent immunization strategy to induce T-cell responses against tumor antigens is to use dendritic cells (DCs) loaded with the ... Full text Link to item Cite

Proteomics for monitoring immune responses to cancer vaccines.

Journal Article Curr Opin Mol Ther · February 2003 Standardized biomarkers for the detection of clinically significant immunological responses would be extremely valuable in immunotherapy trials. Most available assays measure either the frequency or function of antigen-specific T-cells, or the titers of an ... Link to item Cite

Multiple signals are required for maturation of human dendritic cells mobilized in vivo with Flt3 ligand.

Journal Article J Leukoc Biol · September 2002 The ligand for the receptor tyrosine kinase fms-like tyrosine kinase 3 (Flt3L) is a growth factor for hematopoietic progenitors and induces expansion of the two distinct lineages of dendritic cells (DC) that have been described in humans. These two lineage ... Link to item Cite

Dendritic cell recovery following nonmyeloablative allogeneic stem cell transplants.

Journal Article J Hematother Stem Cell Res · August 2002 Nonmyeloablative allogeneic stem cell transplantation (NMSCT) may destroy some malignancies through a graft-versus-tumor (GVT) effect, but tumor relapse and viral reactivation remain challenges for which immunizations may be helpful. Dendritic cells (DC), ... Full text Link to item Cite

Superantigen enhanced protection against a weak tumor-specific melanoma antigen: implications for prophylactic vaccination against cancer.

Journal Article Int J Cancer · December 15, 2001 B16F10 melanoma is a tumor derived from C57BL/6 mice that has been found to be poorly immunogenic and highly aggressive. Here we have shown that vaccination of mice with irradiated B16F10 cells followed by treatment with a combination of staphylococcal ent ... Full text Link to item Cite

Assays for monitoring cellular immune responses to active immunotherapy of cancer.

Journal Article Clin Cancer Res · May 2001 Numerous cancer immunotherapy strategies are currently being tested in clinical trials. Although clinical efficacy will be the final test of these approaches, the long and complicated developmental pathway for these agents necessitates evaluating immunolog ... Link to item Cite

Superantigens: the good, the bad, and the ugly.

Journal Article Exp Biol Med (Maywood) · March 2001 Increasing evidence suggests that superantigens play a role in immune-mediated diseases. Superantigens are potent activators of CD4+ T cells, causing rapid and massive proliferation of cells and cytokine production. This characteristic of superantigens can ... Full text Link to item Cite

Surrogate markers of response to cancer immunotherapy.

Other Expert Opin Biol Ther · March 2001 Clinically effective cancer immunotherapy has been sought for more than 100 years and has been recently applied most successfully in strategies that passively deliver immune effectors such as monoclonal antibodies (anti-CD20 for lymphoma and anti-HER2/neu ... Full text Link to item Cite

Direct detection of cellular immune responses to cancer vaccines.

Journal Article Surgery · March 2001 The evaluation of cancer immunotherapy is predicated on the hypothesis that markers of tumor antigen-specific T-cell immunity will cone-late with clinical efficacy. Establishing which candidate vaccines should enter large-scale clinical trials will necessi ... Full text Link to item Cite

Monitoring cellular immune responses to cancer immunotherapy.

Journal Article Curr Opin Mol Ther · February 2001 Many clinical trials are testing the feasibility of stimulating the immune system to treat cancer. Although the efficacy of this approach will ultimately be determined by clinically relevant endpoints, detection of the magnitude and activity of the immune ... Link to item Cite

Quantitating therapeutically relevant T-cell responses to cancer vaccines.

Journal Article Crit Rev Immunol · 2001 Successful application of active immunotherapy to the treatment of cancer will require stimulation of potent antigen-specific T-cell responses. It is not known how numerous or how potent these T cells must be in order to abrogate tumors, but the levels of ... 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 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

Dendritic cell (DC) reconstitution after nonmyeloablative allogeneic stem cell transplants

Conference Blood · December 1, 2000 Non-myeloablative allogeneic peripheral blood stem cell transplants {mini-allo PBSCT) are being evaluated as a lower toxicity alternative to conventional allogeneic transplantation for harnessing graft versus tumor effects. Induction of anti-tumor immunity ... 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

Down-regulation of neu/HER-2 by interferon-gamma in prostate cancer cells.

Journal Article Cancer Res · July 15, 2000 Interferons (IFNs) are known to possess potent antitumor properties. Previous studies have indicated that IFNs are capable of modulating the expression of various tumor suppressor genes and oncogenes. In this study, we looked at the effect of IFN-gamma on ... Link to item Cite

Type I interferon induction of the Cdk-inhibitor p21WAF1 is accompanied by ordered G1 arrest, differentiation and apoptosis of the Daudi B-cell line.

Journal Article Oncogene · April 9, 1998 We show, in this study, that type I IFN induction of the cyclin-dependent kinase (cdk) inhibitor p21WAF1 in the human Burkitt lymphoma B cell-line Daudi and ensuing cell cycle arrest correlate with the terminal differentiation of these cells, and is ultima ... Full text Link to item Cite

IFNγ induction of P21WAF1 in prostate cancer cells: Role in cell cycle and cell phenotype

Conference FASEB Journal · 1998 Type I and type II interferons (IFNs) are known to exert antitumor effects on a variety of tissues and cell types. We have previously shown that the type I IFN IFNα induces the expression of the cyclin-dependent kinase inhibitor p21 ... Cite

IFNγ inhibition of cell growth in glioblastomas is accompanied by induction of the cyclin dependent kinase inhibitor p21

Conference FASEB Journal · 1998 Glioblastoma is a frequently occurring and highly aggressive form of brain cancer. It is characterized by uncontrolled cell growth caused by a loss of cell cycle regulation, frequently involving mutations in the tumor suppressor genes p53 and p16. In this ... Cite

Interferon induction of the tumor suppressor p21 inhibits cell cycle of tumor cells

Conference FASEB Journal · December 1, 1997 Type I and type II interferons (IFNs) are known to exert anticellular activity on a variety of cell types. We report here on the inhibitory effects of Interferon alpha (IFNa) and interferon gamma (IFN-y) on the cell cycle of the human prostate cancer cell ... Cite

Type I IFN induction of the CDK-inhibitor P21WAF1 is accompanied by ordered G1 arrest, differentiation and apoptosis in the daudi bcell line

Conference FASEB Journal · December 1, 1997 We have previously shown that in the human Burkitt lymphoma B cell-line Oaudi, type I interférons (IFN) induce the expression of the cyclin-dependent kinase (cdk) inhibitor p21 that is linked to the G1 arrest induced by the IFN. Treatment of Daudi cells wi ... Cite

Biochemical effects of type i interferons on prostate cancer cell cycle.

Conference FASEB Journal · December 1, 1996 Prostate cancer is a serious health risk for men that has a marked agerelated increase in incidence. Tumors of the prostate, as with other types of cancer, have been found to be related to the loss of cell cycle control resulting in increased growth of cel ... Cite

A neutralizing epitope of the superantigen SEA has agonist activity on T cells.

Journal Article Biochem Biophys Res Commun · June 25, 1996 We have previously shown that sequence 121-149 of the staphylococcal enterotoxin superantigen SEA plays an important role in superantigen function. A synthetic peptide of this region, SEA(121-149), blocks SEA binding to class II MHC molecules and induces i ... Full text Link to item Cite

The IFN pregnancy recognition hormone IFN-tau blocks both development and superantigen reactivation of experimental allergic encephalomyelitis without associated toxicity.

Journal Article J Immunol · September 1, 1995 Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease if the central nervous system (CNS). Recently, the type I IFN, IFN-beta-1b was demonstrated to be a useful immunotherapy for MS. During treatment with IFN-beta-1b, toxicity at high ... Link to item Cite

Accelerated induction of experimental allergic encephalomyelitis in PL/J mice by a non-V beta 8-specific superantigen.

Journal Article Proc Natl Acad Sci U S A · June 20, 1995 Superantigens such as the staphylococcal enterotoxins can play an important role in exacerbation of autoimmune disorders such as experimental allergic encephalomyelitis (EAE) in mice. In fact, superantigens can reactivate EAE in PL/J mice that have been se ... Full text Link to item Cite