Associate Professor in Pathology
Member of the Duke Cancer Institute
📧 vidyalakshmi.chandramohan@duke.edu
đź“ž Tel: (919) 681 6770
Fax: (919) 684 6791
Open positions in the lab
Graduate Students
We welcome lab rotation applications from Duke University School of Medicine graduate students.
Post-doctoral Fellows
Interested applicants are encouraged to e-mail their resume (three references) and a summary of research interest to vidyalakshmi.chandramohan@duke.edu
Overview
Immunotoxin-based immunotherapies for brain tumors
Here at the Chandramohan Lab, we develop immunotoxin-based novel combinatorial immunotherapies against brain tumors utilizing transplanted brain tumor models in immunocompetent mice and convection-enhanced delivery. We also employ clinical specimens to develop predictive biomarkers to improve patient response to immunotherapies.
Research Initiatives
D2C7-IT is a recombinant antibody fragment derived-immunotoxin (IT) with a high binding affinity for two of the established oncogenes of glioblastoma (GBM), the wild-type epidermal growth factor receptor (EGFRwt) and its mutant EGFR variant III (EGFRvIII). D2C7-IT delivered intratumorally by convection-enhanced delivery demonstrated a potent antitumor response in preclinical animal models of brain tumors. After completion of the D2C7-IT preclinical studies in GBM xenograft models, good laboratory practice-grade D2C7-IT was manufactured at Duke University, and toxicity studies were completed for an FDA-IND application. In an ongoing Phase I dose-escalation/expansion study of D2C7-IT (NCT02303678), we have observed encouraging survival outcomes. The current research is focused on identifying novel therapeutic targets in the tumor microenvironment to enhance the efficacy of D2C7-IT and investigating predictive biomarkers for D2C7-IT in the clinic.
1) Tumor-associated macrophages (TAMs) targeting. TAMs constitute 30-50% of the tumor mass and have been implicated in inhibiting the antitumor T cell response in GBM. The first area of focus of our laboratory is to overcome TAM-mediated immunosuppression and engendering protective T cell responses via CD40 co-stimulation. We have shown in preclinical models that CD40 co-stimulation eliminates TAM suppression, increases T cell infiltration, and increases the antitumor efficacy of D2C7-IT. Ongoing work in preclinical models employs multiparametric flow cytometry, multiplex immunofluorescence, and single-cell RNA sequencing analysis to identify the antigen-presenting cells and elucidate the role of B cells and endothelial cells in D2C7-IT+αCD40 antitumor response.
2) Identifying biomarkers for D2C7-IT/D2C7-IT+αCD40 therapies. To investigate predictive/prognostic immune signatures associated with D2C7-IT or D2C7-IT+αCD40 therapies, we are conducting multiparametric flow cytometry/unsupervised clustering and T cell receptor sequencing analysis of pre and post-treatment peripheral blood mononuclear cells (PBMCs) from patients enrolled in our Phase 1 D2C7-IT (ClinicalTrials.gov Identifier: NCT02303678) and D2C7-IT+αCD40 (ClinicalTrials.gov Identifier: NCT04547777) clinical trials. Identification of biomarkers will aid in the selection of GBM patients who will respond to D2C7-IT or D2C7-IT+αCD40 therapies.
Publications
Gene expression analysis suggests immunosuppressive roles of endolysosomes in glioblastoma.
Sun M. A, Yao H, Yang Q, Pirozzi C. J, Candramohan V, Ashley D. M, He Y. (2023) bioRxiv. Sep 1. doi: https://doi.org/10.1101/2023.08.31.555740
Targeted inhibition of protein synthesis renders cancer cells vulnerable to apoptosis by unfolded protein response.
Gsottberger F, Meier C, Ammon A, Parker S, Wendland K, George R, Petkovic S, Mellenthin L, Emmerich C, Lutzny-Geier G, Metzler M, Mackensen A, Chandramohan V, MĂĽller F. (2023) Cell Death Dis. Aug 26;14(8):561. doi: https://pubmed.ncbi.nlm.nih.gov/37626037/
Ganglioglioma deep transcriptomics reveals primitive neuroectoderm neural precursor-like population.
Regal J. A, Guerra GarcĂa M. E, Jain V, Chandramohan V, Ashley D. M, Gregory S. G, Thompson E. M, LĂłpez G. Y, Reitman Z. J. (2023) Acta Neuropathol Commun. Mar 25;11(1):50. doi: https://pubmed.ncbi.nlm.nih.gov/36966348/. PMID: 36966348
Allergic Asthma Responses Are Dependent on Macrophage Ontogeny.
Tighe R. M, Birukova A, Malakhau Y, Kobayashi Y, Vose A. T, Chandramohan V, Cyphert-Daly J. M, Cumming R. I, Kirshner H. F, Tata P. R, Ingram J. L, Gunn M. D, Que L. G, Yu Y. A. (2023) bioRxiv. Feb 16:2023.02.16.528861. doi: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949163/. Preprint. PMID: 36824904
Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models.
Parker S, McDowall C, Sanchez-Perez L, Osorio C, Duncker P. C, Briley A, Swartz A. M, Herndon 2nd J. E, Yu Y, McLendon R. E, Tedder T. F, Desjardins A, Ashley D. M, Gunn M. D, Enterline D. S, Knorr D. A, Pastan I. H, Nair S. K, Bigner D. D, Chandramohan V. (2023) Sci Transl Med. Feb 8;15(682):eabn5649. doi: https://pubmed.ncbi.nlm.nih.gov/36753564/. PMID: 36753564.
Epigenetic STING silencing is developmentally conserved in gliomas and can be rescued by methyltransferase inhibition.
Low J. T, Chandramohan V, Bowie M. L, Brown M. C, Waitkus M. S, Briley A, Stevenson K, Fuller R, Reitman Z. J, Muscat A. M, Hariharan S, Hostettler S, Danehower S, Baker A, Khasraw M, Wong N. C, Gregory S, Nair S. K, Heimberger A, Gromeier M, Bigner D. D, Ashley D. M. (2022) Cancer Cell. May 9;40(5):439-440. doi: https://pubmed.ncbi.nlm.nih.gov/35487217/. PMID: 35487217.
Th17 Immunity in the colon is controlled by two novel subsets of colon-specific mononuclear phagocytes.
Huang H. I, Jewell M. L, Youssef N, Huang M. N, Hauser E. R, Fee B. E, Rudemiller N. P, Privratsky J. R, Zhang J. J, Reyes E. Y, Wang D, Taylor G. A, Gunn M. D, Ko D. C, Cook D. N, Chandramohan V, Crowley S. D, Hammer G. E. (2021) Front Immunol. Apr 28;12:661290. doi: https://pubmed.ncbi.nlm.nih.gov/33995384/. PMID: 33995384.
Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations.
Chandramohan V, Bao X, Yu X, Parker S, McDowall C, Yu Y. R, Healy P, Desjardins A, Gunn M. D, Gromeier M, Nair S. K, Pastan I. H, Bigner D. D. (2019) J Immunother Cancer. May 29;7(1):142. doi: https://pubmed.ncbi.nlm.nih.gov/31142380/. PMID: 31142380.
Synergistic antitumor effects of 9.2.27-PE38KDEL and ABT-737 in primary and metastatic brain tumors.
Yu X, Dobrikov M, Keir S. T, Gromeier M, Pastan I. H, Reisfeld R, Bigner D. D, Chandramohan V. (2019) PLoS One. Jan 9;14(1):e0210608. doi: https://pubmed.ncbi.nlm.nih.gov/30625226/. PMID: 30625226.
T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma.
Woroniecka K, Chongsathidkeit P, Rhodin K, Kemeny H, Dechant C, Farber S. H, Elsamadicy A. A, Cui X, Koyama S, Jackson C, Hansen L. J, Johanns T. M, Sanchez-Perez L, Chandramohan V, Yu Y. A, Bigner D. D, Giles A, Healy P, Dranoff G, Weinhold K. J, Dunn G. P, Fecci P. E. (2018) Clin Cancer Res. Sep 1;24(17):4175-4186. doi: https://pubmed.ncbi.nlm.nih.gov/29437767/. PMID: 29437767.
Poliovirus Receptor (CD155) Expression in Pediatric Brain Tumors Mediates Oncolysis of Medulloblastoma and Pleomorphic Xanthoastrocytoma.
Thompson E. M, Brown M, Dobrikova E, Ramaswamy V, Taylor M. D, McLendon R, Sanks J, Chandramohan V, Bigner D. D, Gromeier M. (2018) J Neuropathol Exp Neurol. Aug 1:77(8):696-702. doi: https://pubmed.ncbi.nlm.nih.gov/29878245/. PMID: 29878245.
Sym004-induced EGFR elimination is associated with profound anti-tumor activity in EGFRvIII patient-derived glioblastoma models.
Keir S. T, Chandramohan V, Hemphill C. D, Grandal M. M, Melander M. C, Pederson M. W, Horak I. D, Kragh M, Desjardins A, Friedman H. S, Bigner D. D. (2018) J Neurooncol. Jul;138(3):489-498. doi: https://pubmed.ncbi.nlm.nih.gov/29564747/. PMID: 29564747.
Validation of an Immunohistochemistry Assay for Detection of CD155, the Poliovirus Receptor, in Malignant Gliomas.
Chandramohan V, Byrant J. D, Piao H, Keir S. T, Lipp E. S, Lefaivre M, Perkinson K, Bigner D. D, Gromeier M, McLendon R. E. (2017) Arch Pathol Lab Med. Dec;141(12):1697-1704. doi: https://pubmed.ncbi.nlm.nih.gov/28829151/. PMID: 28829151.
Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen-specific CTLs.
Brown M. C, Holl E. K, Boczkowski D, Dobrikova E, Mosaheb M, Chandramohan V, Bigner D. D, Gromeier M, Nair S. K. (2017) Sci Transl Med. Sep 20;9(408):eaan4220. doi: https://pubmed.ncbi.nlm.nih.gov/28931654/. PMID: 28931654.
Selection of novel affinity-matured human chondroitin sulfate proteoglycan 4 antibody fragments by yeast display.
Yu X, Bigner D. D, Chandramohan V. (2017) Protein Eng Des Sel. Sep 1;30(9):639-647. doi: https://pubmed.ncbi.nlm.nih.gov/28981720/. PMID: 28981720.
Production and quality control assessment of a GLP-grade immunotoxin, D2C7-(scdsFv)-PE38KDEL, for a phase I/II clinical trial.
Chandramohan V, Pegram C. N, Piao H, Szafranksi S. E, Kuan C. T, Pastan I. H, Bigner D. D. (2017) Appl Microbiol Biotechnol. Apr;101(7):2747-2766. doi: https://pubmed.ncbi.nlm.nih.gov/28013405/. PMID: 28013405.
Development and validation of a cell-based fluorescent method of measuring antibody affinity.
Yu X, Pegram C. N, Bigner D. D, Chandramohan V. (2017) J Immunol Methods. Mar;442:49-53. doi: https://pubmed.ncbi.nlm.nih.gov/28024998/. PMID: 28024998.
Preclinical toxicity evaluation of a novel immunotoxin, D2C7-(scdsFv)-PE38KDEL, administered via intracerebral convection-enhanced delivery in rats.
Bao X, Chandramohan V, Reynolds R. P, Nortion J. N, Wetsel W. C, Rodriguiz R. M, Aryal D. K, McLendon R. E, Levin E. D, Petry N. A, Zalutsky M. R, Burnett B. K, Kuan C. T, Pastan I. H, Bigner D. D. (2016) Invest New Drugs. Apr;34(2):149-58. doi: https://pubmed.ncbi.nlm.nih.gov/26728879/. PMID: 26728879.
CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains.
Shiina S, Ohno M, Ohka F, Kuramitsu S, Yamamichi A, Kato A, Motomura K, Tanahashi K, Yamamoto T, Watanabe R, Ito I, Senga T, Hamaguchi M, Wakabayashi T, Kaneko M. K, Kato Y, Chandramohan V, Bigner D. D, Natsume A. (2016) Cancer Immunol Res. Mar;4(3):259-68. doi: https://pubmed.ncbi.nlm.nih.gov/26822025/. PMID: 26822025.
Induction of viral, 7-methyl-guanosine cap-independent translation and oncolysis by mitogen-activated protein kinase-interacting kinase-mediate effects on the serine/arginine-rich protein kinase.
Brown M. C, Bryant J. D, Dobrikova E. Y, Shveygert M, Bradrick S. S, Chandramohan V, Bigner D. D, Gromeier M. (2014) J Virol. Nov;88(22):13135-48. doi: https://pubmed.ncbi.nlm.nih.gov/25187541/. PMID: 25187541.
Affinity-matured recombinant immunotoxin targeting gangliosides 3’-isoLM1 and 3’,6’-isoLD1 on malignant gliomas.
Piao H, Kuan C. T, Chandramohan V, Keir S. T, Pegram C. N, Bao X, MĂĄnsson J. E, Pastan I. H, Bigner D. D. (2013) MAbs. Sept-Oct;5(5):748-62. doi: https://pubmed.ncbi.nlm.nih.gov/23924792/. PMID: 23924792.
Construction of an immunotoxin, D2C7-(scdsFv)-PE38KDEL, targeting EGFRwt and EGFRvIII for brain tumor therapy.
Chandramohan V, Bao X, Keir S. T, Pegram C. N, Szafranski S. E, Piao H, Wikstrand C. J, McLendon R. E, Kuan C. T, Pastan I. H, Bigner D. D. (2013) Clin Cancer Res. Sep 1;19(17)4717-27. doi: https://pubmed.ncbi.nlm.nih.gov/23857604/. PMID: 23857604.
Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors.
Chandramohan V, Bao X, Kaneko M. K, Kato Y, Keir S. T, Szafranski S. E, Kuan C. T, Pastan I. H, Bigner D. D. (2013) Int J Cancer. May 15;132(10):2339-48. doi: https://pubmed.ncbi.nlm.nih.gov/23115013/. PMID: 23115013.
Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas.
Kato Y, Vaidyanathan G, Kaneko M. K, Mishima K, Srivastava N, Chandramohan V, Pegram C, Keir S. T, Kuan C. T, Bigner D. D, Zalutsky M. R. (2010) Nucl Med Biol. Oct;37(7):785-94. doi: https://pubmed.ncbi.nlm.nih.gov/20870153/. PMID: 20870153.
GMab-1, a high-affinity anti-3’-isoLM1/3’,6’-isoLD1 IgG monoclonal antibody, raised in lacto-series ganglioside-defective knockout mice.
Kato Y, Kuan C. T, Chang J, Kaneko M. K, Ayriss J, Piao H, Chandramohan V, Pegram C, McLendon R. E, Fredman P, MĂĄnsson J. E, Bigner D. D. (2010) Biochem Biophys Res Commun. Jan 1/391(1):750-5. doi: https://pubmed.ncbi.nlm.nih.gov/19944071/. PMID: 19944071.
c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor.
Chandramohan V, Mineva N. D, Burke B, Jeay S, Wu M, Shen J, Yang W, Hann S. R, Sonenshein G. E. (2008) J Cell Biochem. Aug 15;104(6):2091-106. doi: https://pubmed.ncbi.nlm.nih.gov/18393360/. PMID: 18393360.
Reciprocal control of Forkhead box O 3a and c-Myc via the phosphatidylinositol 3-kinase pathway coordinately regulates p27Kip1 levels.
Chandramohan V, Jeay S, Pianetti S, Sonenshein G. E. (2004) J Immunol. May 1;172(9):5522-7. doi: https://pubmed.ncbi.nlm.nih.gov/15100294/. PMID: 15100294.
Conferences
D2C7 CAR: A novel CAR T cell that simultaneously targets wildtype EGFR and its mutant isoform EGFRvIII for treatment of glioma.
Wilkinson D. S, Ryan K, Wilson J, Chandramohan V, Landi D, Bigner D. D, Fecci P. E. (2022) Journal of Immunology, 208:122.03-122.03. American Association of Immunologists.
Targeted Inhibiton of Protein Biosynthesis sensitizes Cancer Cells to IRE1a-mediated Apoptosis as a Consequence of the unfolded protein response.
Gsottberger F, Meier C, Ammon A, Parker S, Wendland K, George R, Petkovic S, Mellenthin L, Emmerich C, Lutzny-Geier G, Mackensen A, Metzler M, Chandramohan V, Mueller F. (2022) Oncology Research and Treatment, 45:161-161.
Dose Escalation Trial of Fc-Engineered Anti-CD40 Monoclonal Antibody (2141-V11) Administered Intratumorally With d2c7-It via Convection Enhanced Delivery (Ced) for Recurrent Malignant Gliomas (Rmgs)
Desjardins A, Chandaramohan V, Landi D, Peters K. B, Johnson M, Khasraw M, Low J, Threatt S, Bullock C, Herndon J. E, Lipp E. S, Sampson J, Friedman A, Friedman H, Ashley D, Knorr D, Ravetch J, Bigner D. D. (2022) Neuro-oncology, 24:65-65.
A phase 1 trial of D2C7-IT in combination with an Fe-engineered anti-cd40 monoclonal anti-body (2141-V11) administered intratumorally via convection enhanced delivery for adult patients with recurrent malignant glioma (MG).
Desjardins A, Chandramohan V, Landi D. B, Johnson M. O, Khasraw M, Peters K. B, Low J, Herndon J. E, Threatt S, Bullock C. A, Lipp E. S, Sampson J. H, Friedman A. H, Friedman H. S, Ashley D. M, Knorr D, Bigner D. D. (2022) Journal of Clinical Oncology, Vol 40.
Th17 Immunity in the Colon is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes.
Huang H. I, Jewell M. L, Youssef N, Huang M. N, Hauser E. R, Fee B. E, Rudemiller N. P, Privratsky J. R, Zhang J. J, Reyes E. Y, Wang D, Taylor G. A, Gunn M. D, Ko D. C, Cook D. N, Chandramohan V, Crowley S. D, Hammer G. E. (2021) Frontiers in Immunology, 12:661290.
Sting is silenced in gbm by promoter mythlation that is established by tissue of origin.
Low J, Chandramohan V, Bowie M, Brown M, Waitkus M, Briley A, Stevenson K, Fuller R, Reitman Z, Muscat A, Hariharan S, Hostettler J, Wong N, Gromeier M, Ashley D, M. (2021) Neuro-oncology, 23:4-4.
Generation of a third generation cart cells that simultaneously targets wildtype egfr and its mutant isoform egfriii for treatment of glioblastoma.
Wilkinson D, Ryan K, Chandramohan V, Landi D, Bigner D. D, Fecci P. (2021) Neuro-oncology, 23:176-176.
CD226 Expression is Associated with Increased Survival in Pancreatic Cancer.
Landa K, Chandramohan V, Gonen M, Winter J. M, Lidsky M, Shah K, Zani S, Blazer D. G, Gromeier M, McLendon R, Nair S, Allen P. (2020) Annals of Surgical Oncology, 27:S128-S128. SPRINGER.
Sting promoter epigenetic silencing in glioblastoma.
Low J, Bowie M, Chandramohan V, Fuller R, Muscat A, Brown M, Hariharan S, Hostettler J, Briley A, Danehower S, Bake A, Wong N, Ashley D. (2020) Neuro-oncology, 22:73-73.
Phase 1 trial of D2C7 immunotoxin (D2C7-IT) administered intratumorally via convection-enhanced delivery (CED) for recurrent malignant glioma (MG).
Desjardins A, Randazzo D, Chandramohan V, Peters K. B, Johnson M. O, Threatt S, Bullock C. A, Herndon J. E, Healy P, Lipp E. S, Sampson J. H, Friedman A. H, Friedman H. S, Ashley D. M, Bigner D. D. (2020) Journal of Clinical Oncology, Vol 38.
Analysis of immune signatures in pediatric glioblastomas for patient stratification to immunotherapy.
Chandramohan V, Evangelous T, Lipp E, Hora B, Bigner D. D, McLendon R, Ashley D. (2020) Neuro-oncology, 22:365-365.
A PHASE 1 TRIAL OF D2C7-IT IN COMBINATION WITH ATEZOLIZUMAB IN RECURRENT WHO GRADE IV MALIGNANT GLIOMA (MG).
Desjardins A, Randazzo D, Chandramohan V, Peters K, Johnson M, Landi D, Khasraw M, Threatt S, Bullock C, Herndon J, Lipp E, Sampson J, Friedman A, Friedman H, Ashley D, Bigner D, D. (2020) Neuro-oncology, 22:38-38.
DOSE FINDING AND DOSE EXPANSION TRIAL OF D2C7 IMMUNOTOXIN (D2C7-IT) ADMINISTERED INTRATUMORALLY VIA CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMA (MG).
Desjardins A, Randazzo D, Chandramohan V, Peters K, Johnson M, Threatt S, Bullock C, Jackman J, Healy P, Lipp E, Sampson J, Friedman A, Friedman H, Ashley D, Bigner D. D. (2019) Neuro-oncology, 21:vi6-vi6. OXFORD UNIV PRESS INC.
DOSE ESCALATION TRIAL OF D2C7 IMMUNOTOXIN (D2C7-IT) ADMINISTERED INTRATUMORALLY VIA CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMA (MG).
Desjardins A, Randazzo D, Chandramohan V, Peters K, Johnson M, Thomas L, Threatt S, Bullock C, Herndon J, Boulton S, Healy P, Lipp E, Sampson J, Friedman A, Friedman H, Ashley D, Bigner D. D. (2018) Neuro-oncology, 20:vi9-vi9. OXFORD UNIV PRESS INC.
POLIOVIRUS RECEPTOR (CD155) EXPRESSION IN PEDIATRIC BRAIN TUMORS MEDIATES ONCOLYSIS OF MEDULLBLASTOMA AND PLEOMORPHING XANTHOASTROCYTOMA.
Thompson E, Brown M, Dobrikova E, Ramaswamy V, Taylor M, McLendon R, Chandramohan V, Bigner D. D, Gromeier M. (2018) Neuro-oncology, 20:213-213. OXFORD UNIV PRESS INC.
Abstract A79: Cancer immunotherapy with recombinant poliovirus induced IFN-dominant activation of antigen-presenting cells and tumor antigen-specific CTLs.
Brown, M. C, Holl E. K, Boczkowski D, Dobrikova E, Mosaheb M, Chandramohan V, Bigner D. D, Gromeier M, Nair S. K. (2018) Cancer Immunology Research, 6:A79-A79. American Association for Cancer Research (AACR).
Dose escalation study of D2C7-IT administered intratumorally via convection-enhanced delivery for recurrent malignant glioma.
Desjardins A, Randazzo D, Chandramohan V, Peters K. B, Johnson M. O, Threatt S, Herndon J.E, Boulton S, Healy P, Lipp E, Fecci P, Sampson J, Friedman A, Friedman H, Ashley D, Bigner D. (2018) 22nd International Conference on Brain Tumor Research and Therapy.
Dose escalation study of D2C7-IT administered intratumorally via convection-enhanced delivery for recurrent malignant glioma.
Desjardins A, Randazzo D, Chandramohan V, Peters K. B, Johnson M. O, Threatt S, Herndon J.E, Boulton S, Healy P, Lipp E, Fecci P, Sampson J, Friedman A, Friedman H, Ashley D, Bigner D. (2018) 22nd International Conference on Brain Tumor Research and Therapy.
TARGETING EGFR IN HYPOMUTATED PEDIATRIC BRAIN TUMORS USING D2C7 IMMUNOTOXIN.
Landi D, Thompson E, McLendon R, Desjardins A, Chandramohan V, Ashley D. (2018) Neuro-oncology, 20:103-103. OXFORD UNIV PRESS INC.
PVSRIPO is an interferon-resistant, immunotherapeutic oncolytic virus.
Walton R, Brown M, Holl E, Boczkowski D, Chandramohan V, Nair S, Gromeier M. (2017) Journal for Immunotherapy of Cancer, Vol 5. BMC.
Phase 1 single-center, dose escalation study of D2C7-IT administered intratumorally via convection-enhanced delivery for adult patients with recurrent malignant glioma.
Randazzo D, Desjardins A, Chandramohan V, Sampson J. H, Peters K. B, Valhovic G, Threatt S, Herndon J. E, Boulton S, Lally-Goss D, Healy P, Lipp E. S, Friedman A. H, Bigner D. D. (2017) Journal of Clinical Oncology, 35:e13532-e13532. American Society of Clinical Oncology (ASCO).
Immunotoxin and bcl-2 inhibitor combination therapy targeting chondroitin sulfate proteoglycan 4.
Yu X, Keir S. T, Szafranski S, Clayton S, Pastan I, Bigner D. D, Chandramohan V. (2017) Journal of Clinical Oncology, 35:74-74. American Society of Clinical Oncology (ASCO).
A combinatorial immunotherapy for malignant brain tumors: D2C7 immunotoxin and immune checkpoint inhibitors.
Bao X, Keir S. T, Nair S. K, Pastan I, Bigner D. D, Chandramohan V. (2017) Journal of Clinical Oncology, 35:102-102. American Society of Clinical Oncology (ASCO).
Anti-Podoplanin Immunotoxin Therapy For Lung Cancer Treatment.
Xie L, Fan M, Zhang Z, Chandramohan V, Pastan I, Bigner D. D, Bao X. (2017) American Journal of Respiratory and Critical Care Medicine, Vol 195. AMER THORACIC SOC.
PHASE 1 DOSE ESCALATION STUDY OF D2C7-IT ADMINISTERED INTRATUMORALLY VIA CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMA (MG).
Desjardins A, Randazzo D, Chandramohan V, Sampson J, Peters K, Vlahovic G, Threatt S, Herndon J, Boulton S, Lally-Goss D, Healy P, Lipp E, Friedman A, Friedman H, Bigner D. (2016) Neuro-oncology, 18:21-22. OXFORD UNIV PRESS INC.
Abstract A032: Using oncolytic polio expressing tumor as a cancer vaccine.
Mosaheb M. M, Dobrikova E, Brown M. C, Pirozzi C, Chandramohan V, Holl E, Nair S, Gromeier M. (2016) Cancer Immunology Research, 4:A032-A032. American Association for Cancer Research (AACR).
TARGETING IDH1 MUTATIONS USING PEPTIDE VACCINES IN BRAIN TUMORS.
Reap E, Archer G, Sanchez-Perez L, Norberg P, Schmittling R, Nair S, Cui X, Snyder D, Chandramohan V, Choi B, Kuan C. T, Mitchell D, Bigner D, Yan H, Sampson J. (2013) Neuro-oncology, 15:71-71. OXFORD UNIV PRESS INC.
GENERATION OF ANTI-PDGFR alpha IMMUNOTOXINS FOR BRAINSTEM GLIOMA TREATMENT.
Kuan C. T, Chandramohan V, Keir S, Pastan I, Bigner D. (2013) Neuro-oncology, 15:39-40. OXFORD UNIV PRESS INC.
ESTABLISHMENT OF SEVEN NEW PERMANENT PEDIATRIC BRAIN TUMOR LINES.
Keir S, Pegram C, Lipp E, Rasheed A, Chandramohan V, Kuan C. T, Kwatra M, Yan H, Bigner D. (2013) Neuro-oncology, 15:10-10. OXFORD UNIV PRESS INC.
DEVELOPMENT OF A NOVEL SINGLE-CHAIN TRISPECIFIC IMMUNOTOXIN, D2C7-Mel-14-PE38KDEL FOR TARGETED PEDIATRIC BRAIN TUMOR THERAPY.
Chandramohan V, Keir S. T, Bao X, Pastan I. H, Kuan C. T, Bigner D. D. (2013) Neuro-oncology, 15:7-7. OXFORD UNIV PRESS INC.
ESTABLISHMENT OF AND PROOF OF CONCEPT FOR A HUMAN PEDIATRIC BRAINSTEM GLIOMA XENOGRAFT MODEL.
Kuan C. T, Li J, Chandramohan V, Chang J, Bigner D. D. (2011) Neuro-oncology, 13:17-17. OXFORD UNIV PRESS INC.
CONSTRUCTION OF A NOVEL ANTIPODOPLANIN (NZ-1) IMMUNOTOXIN FOR BRAIN TUMOR THERAPY.
Chandramohan V, Kaneko M. K, Kato Y, Pegram C. N, Keir S. T, Pastan I. H, Kuan C. T, Bigner D. D. (2011) Neuro-oncology, 13:126-126. OXFORD UNIV PRESS INC.
Identification of antigens on cancer stem cells for brain tumor therapy.
Chandramohan V, Pegram C. N, Keir S. T, Kuan C. T, Bigner D. D. (2008) Neuro-oncology, 10:384-384. DUKE UNIV PRESS.
Dual-specific antibody, D2C7 (SCDSFV)-PE38KDEL for brain tumor therapy.
Chandramohan V, Pegram C. N, Szafranski S. E, Keir S. T, Pastan I, Kuan C. T, Bigner D. D. (2008) Neuro-oncology, 10:379-379. DUKE UNIV PRESS.
Personnel
Vidya Chandramohan, Ph.D., M.B.A.
Associate Professor in Neurosurgery
Principal Investigator
vidyalakshmi.chandramohan@duke.edu
Dr. Chandramohan is an Associate Professor of Pathology and Neurosurgery at Duke University Medical Center. Dr. Chandramohan received her Bachelor’s degree in Biochemistry with a specialization in Biotechnology at P.S.G. College of Arts and Science, and her Master’s degree in Microbial Gene Technology at Madurai Kamaraj University, India. She then obtained her Ph.D. in Biochemistry with a specialization in Cell and Molecular Biology at Boston University. Dr. Chandramohan then joined the laboratory of Dr. Eli Gilboa at Duke University as a post-doctoral associate to investigate mRNA-transfected dendritic cells as anticancer therapeutics. She continued her post-doctoral training at Duke University under the mentorship of Dr. Darell Bigner, where she developed the dual specific immunotoxin (IT), D2C7-IT, targeting the wild-type epidermal growth factor receptor (EGFRwt) and its mutant EGFR variant III (EGFRvIII), the two common oncogenes of the most malignant brain tumor, glioblastoma (GBM). D2C7-IT is currently in Phase I clinical trials in patients with recurrent GBM and newly diagnosed GBM. In 2020, Dr. Chandramohan obtained her M.B.A. in Data Analytics from North Carolina State University. Her current research includes identifying novel strategies to activate the tumor immune microenvironment to enhance the efficacy of D2C7-IT and investigating immune-related biomarkers to predict the clinical outcome of D2C7-IT and D2C7-IT based combination therapies in patients with GBM. In addition to developing targeted therapies and associated biomarkers, Dr. Chandramohan’s clinical research also focuses on conducting phenotypic and genotypic characterization of tumor and immune cells at the single-cell level in brain tumors by applying multi-omics technology.
Anjali Barnwal, Ph.D.
Post-doctoral Associate
Dr. Barnwal completed her doctoral work under the mentorship of Dr. Jayanta Bhattacharyya at the Centre for Biomedical Engineering, Indian Institute of Technology Delhi, developing dendritic cell-derived extracellular vesicle vaccines for Cancer and COVID-19. In the Chandramohan lab, Dr. Barnwal uses in vitro and in vivo models of brain tumors to study the role of different immune cells: T cells, tumor-associated microglia, B-cells, and macrophage activation by D2C7-IT and αCD40 mono and combination therapy. Dr. Barnwal is also investigating the role of macrophages in brain tumor necrosis by immunohistochemistry and spatial transcriptomics using patient specimens.
Cristina Osorio
Research Analyst/Research Animal Coordinator/Lab Manager
Cristina obtained her B.S. in Psychology from the University of San Buenaventura, Colombia, SA. She has 20+ years of experience in lab management and proteomics/molecular biology research. In the Chandramohan lab, Cristina is in charge of animal protocol amendments, transgenic mice colony management, and performing in vivo mechanistic studies to delineate the role of myeloid cells in brain tumor growth and antitumor response.
Edwige Edouard
Research Technician II
Ed obtained his B.S. in Biology from the University of the District of Columbia. He has 15+ years of experience in animal handling, breeding, and surgery. In the Chandramohan lab, Ed is in charge of breeding and performing in vivo brain tumor therapy studies by convection-enhanced delivery.
Hunter Jackson
Research Technician II
Hunter obtained their B.S. in Biology (minor in Jewish Studies) from St. Edward’s University, Austin, TX. In the Chandramohan lab, Hunter is in charge of breeding, monitoring study mice, immunohistochemistry analysis, and assisting in vivo brain tumor therapy studies.
William Yan
Student Research Assistant
William is an undergraduate student in the Biomedical Engineering program at Duke University. In the Chandramohan lab, William uses in vivo models of brain tumors in immunocompetent mice to investigate the role of αVEGF and endothelial cells in the D2C7-IT and αCD40 combination therapy-induced antitumor response.