Scholars@Duke
Vidyalakshmi Chandramohan

Vidyalakshmi Chandramohan

Associate Professor in Neurosurgery
Neurosurgery, Neuro-Oncology
Vidyalakshmi.Chandramohan@duke.edu
Box 3156 Med Ctr, Durham, NC 27710
185 MSRB, Durham, NC 27710

Selected Publications

Gene expression analysis suggests immunosuppressive roles of endolysosomes in glioblastoma.

Journal Article PLoS One · 2024 Targeting endolysosomes is a strategy extensively pursued for treating cancers, including glioblastomas (GBMs), on the basis that the intact function of these subcellular organelles is key to tumor cell autophagy and survival. Through gene expression analy ... Full text Link to item Cite

Altered ontogeny and transcriptomic signatures of tissue-resident pulmonary interstitial macrophages ameliorate allergic airway hyperresponsiveness.

Journal Article Front Immunol · 2024 INTRODUCTION: Environmental exposures and experimental manipulations can alter the ontogenetic composition of tissue-resident macrophages. However, the impact of these alterations on subsequent immune responses, particularly in allergic airway diseases, re ... Full text Link to item Cite

Targeted inhibition of protein synthesis renders cancer cells vulnerable to apoptosis by unfolded protein response.

Journal Article Cell Death Dis · August 26, 2023 Cellular stress responses including the unfolded protein response (UPR) decide over the fate of an individual cell to ensure survival of the entire organism. During physiologic UPR counter-regulation, protective proteins are upregulated to prevent cell dea ... Full text Link to item Cite

LGG-13. GANGLIOGLIOMA DEEP TRANSCRIPTOMICS REVEALS A CD34+ PRIMITIVE NEUROECTODERM NEURAL PRECURSOR-LIKE POPULATION

Conference Neuro-Oncology · June 12, 2023 AbstractGangliogliomas are glioneuronal brain tumors that typically present in childhood or early adulthood. Though most often low-grade, new insights are needed to refine glioneuronal tumor classification a ... Full text Cite

Ganglioglioma deep transcriptomics reveals primitive neuroectoderm neural precursor-like population.

Journal Article Acta Neuropathol Commun · March 25, 2023 Gangliogliomas are brain tumors composed of neuron-like and macroglia-like components that occur in children and young adults. Gangliogliomas are often characterized by a rare population of immature astrocyte-appearing cells expressing CD34, a marker expre ... 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

D2C7 CAR: A novel CAR T cell that simultaneously targets wildtype EGFR and its mutant isoform EGFRvIII for treatment of glioma

Conference The Journal of Immunology · May 1, 2022 AbstractBrain tumors are the leading cause of cancer death in children and a significant cause of morbidity and mortality in adults. Conventional treatments are suboptimal, thus signifying the need for novel ... Full text Cite

A phase 1 trial of D2C7-it in combination with an Fc-engineered anti-CD40 monoclonal antibody (2141-V11) administered intratumorally via convectionenhanced delivery for adult patients with recurrent malignant glioma (MG).

Conference JOURNAL OF CLINICAL ONCOLOGY · 2022 Background: D2C7 immunotoxin (D2C7-IT) is a dual-specific recombinant immunotoxin comprising an EGFR wild-type and mutant-specific (EGFRvIII) monoclonal antibody (Ab) fragment and a genetically engineered form of the Pseudomonas exotoxin. When injected dir ... Full text Link to item Cite

Th17 Immunity in the Colon Is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes.

Conference Front Immunol · 2021 Intestinal immunity is coordinated by specialized mononuclear phagocyte populations, constituted by a diversity of cell subsets. Although the cell subsets constituting the mononuclear phagocyte network are thought to be similar in both small and large inte ... Full text Link to item Cite

CD226 Expression is Associated with Increased Survival in Pancreatic Cancer

Conference ANNALS OF SURGICAL ONCOLOGY · February 1, 2020 Link to item 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

Synergistic antitumor effects of 9.2.27-PE38KDEL and ABT-737 in primary and metastatic brain tumors.

Journal Article PLoS One · 2019 Standard treatment, unfortunately, yields a poor prognosis for patients with primary or metastatic cancers in the central nervous system, indicating a necessity for novel therapeutic agents. Immunotoxins (ITs) are a class of promising therapeutic candidate ... Full text Open Access Link to item Cite

T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma.

Journal Article Clin Cancer Res · September 1, 2018 Purpose: T-cell dysfunction is a hallmark of glioblastoma (GBM). Although anergy and tolerance have been well characterized, T-cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoin ... 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

Poliovirus Receptor (CD155) Expression in Pediatric Brain Tumors Mediates Oncolysis of Medulloblastoma and Pleomorphic Xanthoastrocytoma.

Journal Article J Neuropathol Exp Neurol · August 1, 2018 Poliovirus oncolytic immunotherapy is a putatively novel approach to treat pediatric brain tumors. This work sought to determine expression of the poliovirus receptor (PVR), CD155, in low-grade and malignant pediatric brain tumors and its ability to infect ... Full text Link to item Cite

Sym004-induced EGFR elimination is associated with profound anti-tumor activity in EGFRvIII patient-derived glioblastoma models.

Journal Article J Neurooncol · July 2018 BACKGROUND: Sym004 is a mixture of two monoclonal antibodies (mAbs), futuximab and modotuximab, targeting non-overlapping epitopes on the epidermal growth factor receptor (EGFR). Previous studies have shown that Sym004 is more efficient at inducing interna ... Full text Open Access Link to item Cite

Validation of an Immunohistochemistry Assay for Detection of CD155, the Poliovirus Receptor, in Malignant Gliomas.

Journal Article Arch Pathol Lab Med · December 2017 CONTEXT: - The oncolytic polio-rhinovirus recombinant (PVSRIPO) has demonstrated promise in currently ongoing phase I/II clinical trials against recurrent glioblastoma and was granted breakthrough therapy designation by the Food and Drug Administration/Cen ... Full text Link to item Cite

PVSRIPO is an interferon-resistant, immunotherapeutic oncolytic virus

Conference JOURNAL FOR IMMUNOTHERAPY OF CANCER · November 7, 2017 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 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

Selection of novel affinity-matured human chondroitin sulfate proteoglycan 4 antibody fragments by yeast display.

Journal Article Protein Eng Des Sel · September 1, 2017 Chondroitin sulfate proteoglycan 4 (CSPG4) is a promising target for cancer immunotherapy due to its high level of expression in a number of malignant tumors, and its essential role in tumor growth and progression. Clinical application of CSPG4-targeting i ... Full text Link to item Cite

Phase 1 single-center, dose escalation study of D2C7-IT administered intratumorally via convection-enhanced delivery for adult patients with recurrent malignant glioma.

Conference Journal of Clinical Oncology · May 20, 2017 e13532 Background: D2C7 immunotoxin (D2C7-IT) is a dual-specific recombinant immunotoxin consisting of EGFR-wt and EGFRvIII monoclonal antibodies with a genetically engineered Pseudomonas exotoxin, PE-38KDEL. The primary objectiv ... Full text Link to item Cite

Production and quality control assessment of a GLP-grade immunotoxin, D2C7-(scdsFv)-PE38KDEL, for a phase I/II clinical trial.

Journal Article Appl Microbiol Biotechnol · April 2017 D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel recombinant Pseudomonas exotoxin A-based immunotoxin (IT), targeting both wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins overexpressed in glioblastomas. Initia ... Full text Link to item Cite

Immunotoxin Therapy for Brain Tumors

Chapter · March 2, 2017 Despite a multimodal approach involving surgery, radiotherapy, and chemotherapy, the median survival for malignant brain tumor patients is limited to 15-19. months. To improve glioblastoma patient survival, novel therapies targeting the heterogeneous tumor ... Full text Cite

Preclinical Immunotherapeutic Animal Models for Brain Tumors

Chapter · March 2, 2017 Glioblastoma (GBM) is the most malignant primary brain tumor in adults. Even with the current standard of care therapy (i.e., surgery, radiotherapy, and chemotherapy), GBM has a poor prognosis. Innovative immunotherapeutic approaches, which engage a patien ... Full text Cite

Development and validation of a cell-based fluorescent method for measuring antibody affinity.

Journal Article J Immunol Methods · March 2017 Monoclonal antibodies have become essential tools for diagnostic and therapeutic purposes. Antibody affinity is one of the critical factors influencing the therapeutic success of tumor-targeting antibodies. Therefore, developing an accurate and reliable me ... 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

Immunotoxin and bcl-2 inhibitor combination therapy targeting chondroitin sulfate proteoglycan 4.

Conference Journal of Clinical Oncology · March 1, 2017 74 Background: Immunotoxins (ITs) are a class of bifunctional chimeric proteins composed of an antibody fragment linked to a toxin. When ITs internalize into target cells, they induce protein synthesis inhibition and apoptosis. W ... Full text Cite

Anti-Podoplanin Immunotoxin Therapy For Lung Cancer Treatment

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2017 Link to item Cite

Abstract A032: Using oncolytic polio expressing tumor as a cancer vaccine

Conference Cancer Immunology Research · November 1, 2016 AbstractBackground: The recent clinical success of immune checkpoint inhibitors in melanoma revealed the therapeutic potential of an anti-tumor T cell response. Previous studies using peptide vaccines to eli ... Full text Cite

Preclinical toxicity evaluation of a novel immunotoxin, D2C7-(scdsFv)-PE38KDEL, administered via intracerebral convection-enhanced delivery in rats.

Journal Article Invest New Drugs · April 2016 D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel immunotoxin that reacts with wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFRvIII proteins overexpressed in glioblastomas. This study assessed the toxicity of intracerebral administration of D2 ... Full text Link to item Cite

CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains.

Journal Article Cancer Immunol Res · March 2016 Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults with a 5-year overall survival rate of less than 10%. Podoplanin (PDPN) is a type I transmembrane mucin-like glycoprotein, expressed in the lymphatic endothelium. Seve ... Full text Link to item Cite

Induction of viral, 7-methyl-guanosine cap-independent translation and oncolysis by mitogen-activated protein kinase-interacting kinase-mediated effects on the serine/arginine-rich protein kinase.

Journal Article J Virol · November 2014 UNLABELLED: Protein synthesis, the most energy-consuming process in cells, responds to changing physiologic priorities, e.g., upon mitogen- or stress-induced adaptations signaled through the mitogen-activated protein kinases (MAPKs). The prevailing status ... Full text Link to item Cite

Idh1 mutations as a immunotherapeutic target for brain tumors.

Journal Article Neuro Oncol · July 2014 Immunotherapy promises an exquisitely precise therapeutic approach, and substantial evidence suggests that activated T cells can eradicate large tumors, even within the "immunologically privileged" brain. EGFRvIII and isocitrate dehydrogenase 1 (IDH1) muta ... Full text Link to item Cite

A novel recombinant immunotoxin-based therapy targeting wild-type and mutant EGFR improves survival in murine models of glioblastoma.

Journal Article Oncoimmunology · December 1, 2013 Both the amplification of the gene coding for wild-type (wt) epidermal growth factor receptor (EGFR) and the overexpression of the EGFR deletion mutant, commonly known as EGFRvIII, are hallmarks of glioblastoma. We have recently reported a novel, recombina ... Full text Open Access Link to item Cite

A novel recombinant immunotoxin-based therapy targeting wild-type and mutant EGFR improves survival in murine models of glioblastoma

Journal Article OncoImmunology · December 1, 2013 Both the amplification of the gene coding for wild-type (wt) epidermal growth factor receptor (EGFR) and the overexpression of the EGFR deletion mutant, commonly known as EGFRvIII, are hallmarks of glioblastoma. We have recently reported a novel, recombina ... Full text Cite

Construction of an immunotoxin, D2C7-(scdsFv)-PE38KDEL, targeting EGFRwt and EGFRvIII for brain tumor therapy.

Journal Article Clin Cancer Res · September 1, 2013 PURPOSE: The EGF receptor gene (EGFR) is most frequently amplified and overexpressed, along with its deletion mutant, EGFRvIII, in glioblastoma. We tested the preclinical efficacy of the recombinant immunotoxin, D2C7-(scdsFv)-PE38KDEL, which is reactive wi ... Full text Link to item Cite

Antibody, T-cell and dendritic cell immunotherapy for malignant brain tumors.

Journal Article Future Oncol · July 2013 Modest improvement in brain tumor patient survival has been achieved through advances in surgical, adjuvant radiation and chemotherapeutic strategies. However, these traditional approaches have been unsuccessful in permanently controlling these aggressive ... Full text Link to item Cite

Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors.

Journal Article Int J Cancer · May 15, 2013 Our study demonstrates the glioma tumor antigen podoplanin to be present at very high levels (>90%) in both glioblastoma (D2159MG, D08-0308MG and D08-0493MG) and medulloblastoma (D283MED, D425MED and DAOY) xenografts and cell line. We constructed a novel r ... Full text Link to item Cite

Current immunotherapeutic targets in gliomas

Journal Article · May 1, 2013 The prospect for high-grade astrocytic tumor patients continues to be dismal, evenwith advances in surgery, radiotherapy, and chemotherapy. There is a need for thedevelopment of novel therapies that would eliminate the heterogeneous and diffuseastrocytic t ... Cite

Affinity-matured recombinant immunotoxin targeting gangliosides 3'-isoLM1 and 3',6'-isoLD1 on malignant gliomas.

Journal Article MAbs · 2013 About 60 percent of glioblastomas highly express the gangliosides 3'-isoLM1 and 3',6'-isoLD1 on the cell surface, providing ideal targets for brain tumor immunotherapy. A novel recombinant immunotoxin, DmAb14m-(scFv)-PE38KDEL (DmAb14m-IT), specific for the ... Full text Link to item Cite

Toxin-based targeted therapy for malignant brain tumors.

Journal Article Clin Dev Immunol · 2012 Despite advances in conventional treatment modalities for malignant brain tumors-surgery, radiotherapy, and chemotherapy-the prognosis for patients with high-grade astrocytic tumor remains dismal. The highly heterogeneous and diffuse nature of astrocytic t ... Full text Open Access Link to item Cite

Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas.

Journal Article Nucl Med Biol · October 2010 INTRODUCTION: Podoplanin/aggrus is a mucin-like sialoglycoprotein that is highly expressed in malignant gliomas. Podoplanin has been reported to be a novel marker to enrich tumor-initiating cells, which are thought to resist conventional therapies and to b ... Full text Link to item Cite

GMab-1, a high-affinity anti-3'-isoLM1/3',6'-isoLD1 IgG monoclonal antibody, raised in lacto-series ganglioside-defective knockout mice.

Journal Article Biochem Biophys Res Commun · January 1, 2010 The lacto-series gangliosides 3'-isoLM1 and 3',6'-isoLD1 have been identified as tumor-associated antigens whose formation is initiated by the Lc3-synthase. Until now, high-affinity IgG monoclonal antibodies (mAbs) against 3'-isoLM1 and 3',6'-isoLD1, which ... Full text Link to item Cite

c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor.

Journal Article J Cell Biochem · August 15, 2008 The p27(Kip1) (p27) cyclin-dependent kinase inhibitor and c-Myc oncoprotein play essential roles in control of cell cycle progression and apoptosis. Induction of p27 (CDKN1B) gene transcription by Forkhead box O proteins such as FOXO3a leads to growth arre ... Full text Link to item Cite

Reciprocal control of Forkhead box O 3a and c-Myc via the phosphatidylinositol 3-kinase pathway coordinately regulates p27Kip1 levels.

Journal Article J Immunol · May 1, 2004 B cell receptor (BCR) engagement of murine WEHI 231 immature B lymphoma cells leads sequentially to a drop in NF-kappa B and c-Myc, and induction of the p27(Kip1) cyclin-dependent kinase inhibitor, which promotes growth arrest and apoptosis. BCR engagement ... Full text Link to item Cite