Bio

Current Role at Stanford


Senior Scientist.
Research Team leader, brain tumor and human neural stem cell research
Adult and Pediatric brain tumor CD47 therapeutic development group

Education & Certifications


  • Ph.D., University at Buffalo, The State University of New York, Molecular and Cellular Biology (2005)
  • M.S., SUNY Buffalo, Molecular Cell Biology (2002)
  • M.Sc. (Hons), Panjab University, India. Basic Medical Sciences (Honors School), Biophysics (Honors) (1999)
  • B.Sc. (Hons), Panjab University, India. Basic Medical Sciences (Honors School), Biophysics (Honors) (1997)

Projects


  • Identifying the developmental lineage in human fetal brain development, Stanford University, Institute of Stem Cell Biology and Regenerative Medicine (5/11/2012)

    Location

    Stanford University

  • Delineating the Cancer Stem Cell Hierarchy in human high grade brain tumors, Stanford University, Institute of Stem Cell Biology and Regenerative Medicine (5/11/2012 - Present)

    Location

    Stanford University

    Collaborators

  • Novel immunotherapies for pediatric brain tumors, Stanford Institute of Stem Cell Biology and Regenerative Medicine (5/11/2012 - Present)

    Location

    Stanford University

    Collaborators

Professional

Professional Interests


Cancer Stem Cells,
Development of antibody therapeutics against brain tumors,
Identification of the developmental hierarchy in human fetal brain development

Work Experience


  • Postdoctoral Fellow, University of California, Davis (3/1/2005 - 12/31/2006)

    1. Dissociation and culture of primary neurons from hippocampus, Cortex, spinal cord and Superior Cervical Ganglion from neonatal mouse brains
    2. Dissociation and culture of neonatal cardiomyocytes

    Location

    Davis, CA

  • Research Associate, Stanford Institute of Stem Cell Biology and Regenerative Medicine (January 1, 2010 - May 1, 2011)

    Prospective isolation of brain tumor initiating cells.
    Development of anti-CD47 immunotherapy against human brain tumors

    Location

    Stanford University

Professional Affiliations and Activities


  • Member, Society for NeuroOncology (2009 - Present)
  • member, American Association of Cancer Research (2007 - Present)
  • Member, American Society for Cell Biology (2004 - Present)

Publications

Journal Articles


  • Targeting a Glioblastoma Cancer Stem-Cell Population Defined by EGF Receptor Variant III. Cancer research Emlet, D. R., Gupta, P., Holgado-Madruga, M., Del Vecchio, C. A., Mitra, S. S., Han, S., Li, G., Jensen, K. C., Vogel, H., Xu, L. W., Skirboll, S. S., Wong, A. J. 2014; 74 (4): 1238-1249

    Abstract

    The relationship between mutated proteins and the cancer stem cell population is unclear. Glioblastoma tumors frequently express EGFRvIII, an EGFR variant that arises via gene rearrangement and amplification. However, expression of EGFRvIII is restricted despite the prevalence of the alteration. Here we show that EGFRvIII is highly co-expressed with CD133 and that EGFRvIII+/CD133+ defines the population of cancer stem cells with the highest degree of self-renewal and tumor initiating ability. EGFRvIII+ cells are associated with other stem/progenitor markers while markers of differentiation are found in EGFRvIII- cells. EGFRvIII expression is lost in standard cell culture but its expression is maintained in tumor sphere culture, and cultured cells also retain the EGFRvIII+/CD133+ co-expression and self-renewal and tumor initiating abilities. Elimination of the EGFRvIII+/CD133+ population using a bispecific antibody reduced tumorigenicity of implanted tumor cells better than any reagent directed against a single epitope. This work demonstrates that a mutated oncogene can have CSC specific expression and be used to specifically target this population.

    View details for DOI 10.1158/0008-5472.CAN-13-1407

    View details for PubMedID 24366881

  • BET Bromodomain Inhibition of MYC-Amplified Medulloblastoma. Clinical cancer research Bandopadhayay, P., Bergthold, G., Nguyen, B., Schubert, S., Gholamin, S., Tang, Y., Bolin, S., Schumacher, S. E., Zeid, R., Masoud, S., Yu, F., Vue, N., Gibson, W. J., Paolella, B. R., Mitra, S. S., Cheshier, S. H., Qi, J., Liu, K., Wechsler-Reya, R., Weiss, W. A., Swartling, F. J., Kieran, M. W., Bradner, J. E., Beroukhim, R., Cho, Y. 2014; 20 (4): 912-925

    Abstract

    MYC-amplified medulloblastomas are highly lethal tumors. BET bromodomain inhibition has recently been shown to suppress MYC-associated transcriptional activity in other cancers. The compound JQ1 inhibits BET bromodomain-containing proteins, including BRD4. Here we investigate BET bromodomain targeting for the treatment of MYC-amplified medulloblastoma.We evaluated the effects of genetic and pharmacological inhibition of BET bromodomains on proliferation, cell cycle, and apoptosis in established and newly generated patient- and GEMM-derived medulloblastoma cell lines and xenografts that harbored amplifications of MYC or MYCN. We also assessed the effect of JQ1 on MYC expression and global MYC-associated transcriptional activity. We assessed in vivo efficacy of JQ1 in orthotopic xenografts established in immunocompromised mice.Treatment of MYC-amplified medulloblastoma cells with JQ1 decreased cell viability associated with arrest at G1 and apoptosis. We observed down-regulation of MYC expression and confirmed inhibition of MYC-associated transcriptional targets. Exogenous expression of MYC from a retroviral promoter reduced the effect of JQ1 on cell viability, suggesting that attenuated levels of MYC contribute to the functional effects of JQ1. JQ1 significantly prolonged survival of orthotopic xenograft models of MYC-amplified medulloblastoma (p<0.001). Xenografts harvested from mice after five doses of JQ1 had reduced expression of MYC mRNA and a reduced proliferative index.JQ1 suppresses MYC expression and MYC-associated transcriptional activity in medulloblastomas, resulting in an overall decrease in medulloblastoma cell viability. These preclinical findings highlight the promise of BET bromodomain inhibitors as novel agents for MYC-amplified medulloblastoma.

    View details for DOI 10.1158/1078-0432.CCR-13-2281

    View details for PubMedID 24297863

  • Roles of PINK1, mTORC2, and mitochondria in preserving brain tumor-forming stem cells in a noncanonical Notch signaling pathway. Genes & development Lee, K., Wu, Z., Song, Y., Mitra, S. S., Feroze, A. H., Cheshier, S. H., Lu, B. 2013; 27 (24): 2642-2647

    Abstract

    The self-renewal versus differentiation choice of Drosophila and mammalian neural stem cells (NSCs) requires Notch (N) signaling. How N regulates NSC behavior is not well understood. Here we show that canonical N signaling cooperates with a noncanonical N signaling pathway to mediate N-directed NSC regulation. In the noncanonical pathway, N interacts with PTEN-induced kinase 1 (PINK1) to influence mitochondrial function, activating mechanistic target of rapamycin complex 2 (mTORC2)/AKT signaling. Importantly, attenuating noncanonical N signaling preferentially impaired the maintenance of Drosophila and human cancer stem cell-like tumor-forming cells. Our results emphasize the importance of mitochondria to N and NSC biology, with important implications for diseases associated with aberrant N signaling.

    View details for DOI 10.1101/gad.225169.113

    View details for PubMedID 24352421

  • Usp16 contributes to somatic stem-cell defects in Down's syndrome. Nature Adorno, M., Sikandar, S., Mitra, S. S., Kuo, A., Nicolis Di Robilant, B., Haro-Acosta, V., Ouadah, Y., Quarta, M., Rodriguez, J., Qian, D., Reddy, V. M., Cheshier, S., Garner, C. C., Clarke, M. F. 2013; 501 (7467): 380-384

    Abstract

    Down's syndrome results from full or partial trisomy of chromosome 21. However, the consequences of the underlying gene-dosage imbalance on adult tissues remain poorly understood. Here we show that in Ts65Dn mice, which are trisomic for 132 genes homologous to genes on human chromosome 21, triplication of Usp16 reduces the self-renewal of haematopoietic stem cells and the expansion of mammary epithelial cells, neural progenitors and fibroblasts. In addition, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts. Usp16 can remove ubiquitin from histone H2A on lysine 119, a critical mark for the maintenance of multiple somatic tissues. Downregulation of Usp16, either by mutation of a single normal Usp16 allele or by short interfering RNAs, largely rescues all of these defects. Furthermore, in human tissues overexpression of USP16 reduces the expansion of normal fibroblasts and postnatal neural progenitors, whereas downregulation of USP16 partially rescues the proliferation defects of Down's syndrome fibroblasts. Taken together, these results suggest that USP16 has an important role in antagonizing the self-renewal and/or senescence pathways in Down's syndrome and could serve as an attractive target to ameliorate some of the associated pathologies.

    View details for DOI 10.1038/nature12530

    View details for PubMedID 24025767

  • Coregulation of Multiple Signaling Mechanisms in pp60v-Src-Induced Closure of Cx43 Gap Junction Channels JOURNAL OF MEMBRANE BIOLOGY Mitra, S. S., Xu, J., Nicholson, B. J. 2012; 245 (8): 495-506

    Abstract

    Attenuation in gap junctional coupling has consistently been associated with induction of rapid or synchronous cell division in normal and pathological conditions. In the case of the v-src oncogene, gating of Cx43 gap junction channels has been linked to both direct phosphorylation of tyrosines (Y247 and 265) and phosphorylation of the serine targets of Erk1/2 (S255, 279 and 282) on the cytoplasmic C-terminal domain of Cx43. However, only the latter has been associated with acute, rather than chronic, gating of the channels immediately after v-src expression, a process that is mediated through a "ball-and-chain" mechanism. In this study we show that, while ERK1/2 is necessary for acute closure of gap junction channels, it is not sufficient. Rather, multiple pathways converge to regulate Cx43 coupling in response to expression of v-src, including parallel signaling through PKC and MEK1/2, with additional positive and negative regulatory effects mediated by PI3 kinase, distinguished by the involvement of Akt.

    View details for DOI 10.1007/s00232-012-9500-0

    View details for Web of Science ID 000309207800007

    View details for PubMedID 22965738

  • Expression of epidermal growth factor variant III (EGFRvIII) in pediatric diffuse intrinsic pontine gliomas JOURNAL OF NEURO-ONCOLOGY Li, G., Mitra, S. S., Monje, M., Henrich, K. N., Bangs, C. D., Nitta, R. T., Wong, A. J. 2012; 108 (3): 395-402

    Abstract

    Despite numerous clinical trials over the past 2 decades, the overall survival for children diagnosed with diffuse intrinsic pontine glioma (DIPG) remains 9-10 months. Radiation therapy is the only treatment with proven effect and novel therapies are needed. Epidermal growth factor receptor variant III (EGFRvIII) is the most common variant of the epidermal growth factor receptor and is expressed in many tumor types but is rarely found in normal tissue. A peptide vaccine targeting EGFRvIII is currently undergoing investigation in phase 3 clinical trials for the treatment of newly diagnosed glioblastoma (GBM), the tumor in which this variant receptor was first discovered. In this study, we evaluated EGFRvIII expression in pediatric DIPG samples using immunohistochemistry with a double affinity purified antibody raised against the EGFRvIII peptide. Staining of pediatric DIPG histological samples revealed expression in 4 of 9 cases and the pattern of staining was consistent with what has been seen in EGFRvIII transfected cells as well as GBMs from adult trials. In addition, analysis of tumor samples collected immediately post mortem and of DIPG cells in culture by RT-PCR, western blot analysis, and flow cytometry confirmed EGFRvIII expression. We were therefore able to detect EGFRvIII expression in 6 of 11 DIPG cases. These data suggest that EGFRvIII warrants investigation as a target for these deadly pediatric tumors.

    View details for DOI 10.1007/s11060-012-0842-3

    View details for Web of Science ID 000305123800007

    View details for PubMedID 22382786

  • The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Willingham, S. B., Volkmer, J., Gentles, A. J., Sahoo, D., Dalerba, P., Mitra, S. S., Wang, J., Contreras-Trujillo, H., Martin, R., Cohen, J. D., Lovelace, P., Scheeren, F. A., Chao, M. P., Weiskopf, K., Tang, C., Volkmer, A. K., Naik, T. J., Storm, T. A., Mosley, A. R., Edris, B., Schmid, S. M., Sun, C. K., Chua, M., Murillo, O., Rajendran, P., Cha, A. C., Chin, R. K., Kim, D., Adorno, M., Raveh, T., Tseng, D., Jaiswal, S., Enger, P. O., Steinberg, G. K., Li, G., So, S. K., Majeti, R., Harsh, G. R., van de Rijn, M., Teng, N. N., Sunwoo, J. B., Alizadeh, A. A., Clarke, M. F., Weissman, I. L. 2012; 109 (17): 6662-6667

    Abstract

    CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRP?, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.

    View details for DOI 10.1073/pnas.1121623109

    View details for Web of Science ID 000303249100065

    View details for PubMedID 22451913

  • Heterogeneous reallocation of presynaptic efficacy in recurrent excitatory circuits adapting to inactivity. Nature neuroscience Mitra, A., Mitra, S. S., Tsien, R. W. 2012; 15 (2): 250-257

    Abstract

    Recurrent excitatory circuits face extreme challenges in balancing efficacy and stability. We recorded from CA3 pyramidal neuron pairs in rat hippocampal slice cultures to characterize synaptic and circuit-level changes in recurrent synapses resulting from long-term inactivity. Chronic tetrodotoxin treatment greatly reduced the percentage of connected CA3-CA3 neurons, but enhanced the strength of the remaining connections; presynaptic release probability sharply increased, whereas quantal size was unaltered. Connectivity was decreased in activity-deprived circuits by functional silencing of synapses, whereas three-dimensional anatomical analysis revealed no change in spine or bouton density or aggregate dendrite length. The silencing arose from enhanced Cdk5 activity and could be reverted by acute Cdk5 inhibition with roscovitine. Our results suggest that recurrent circuits adapt to chronic inactivity by reallocating presynaptic weights heterogeneously, strengthening certain connections while silencing others. This restricts synaptic output and input, preserving signaling efficacy among a subset of neuronal ensembles while protecting network stability.

    View details for DOI 10.1038/nn.3004

    View details for PubMedID 22179109

  • Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Monje, M., Mitra, S. S., Freret, M. E., Raveh, T. B., Kim, J., Masek, M., Attema, J. L., Li, G., Haddix, T., Edwards, M. S., Fisher, P. G., Weissman, I. L., Rowitch, D. H., Vogel, H., Wong, A. J., Beachy, P. A. 2011; 108 (11): 4453-4458

    Abstract

    Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive tumors of childhood that are almost universally fatal. Our understanding of this devastating cancer is limited by a dearth of available tissue for study and by the lack of a faithful animal model. Intriguingly, DIPGs are restricted to the ventral pons and occur during a narrow window of middle childhood, suggesting dysregulation of a postnatal neurodevelopmental process. Here, we report the identification of a previously undescribed population of immunophenotypic neural precursor cells in the human and murine brainstem whose temporal and spatial distributions correlate closely with the incidence of DIPG and highlight a candidate cell of origin. Using early postmortem DIPG tumor tissue, we have established in vitro and xenograft models and find that the Hedgehog (Hh) signaling pathway implicated in many developmental and oncogenic processes is active in DIPG tumor cells. Modulation of Hh pathway activity has functional consequences for DIPG self-renewal capacity in neurosphere culture. The Hh pathway also appears to be active in normal ventral pontine precursor-like cells of the mouse, and unregulated pathway activity results in hypertrophy of the ventral pons. Together, these findings provide a foundation for understanding the cellular and molecular origins of DIPG, and suggest that the Hh pathway represents a potential therapeutic target in this devastating pediatric tumor.

    View details for DOI 10.1073/pnas.1101657108

    View details for Web of Science ID 000288450900040

    View details for PubMedID 21368213

  • The role of the c-Jun N-terminal kinase 2-alpha-isoform in non-small cell lung carcinoma tumorigenesis ONCOGENE Nitta, R. T., Del Vecchio, C. A., Chu, A. H., Mitra, S. S., Godwin, A. K., Wong, A. J. 2011; 30 (2): 234-244

    Abstract

    The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase family and have been implicated in tumorigenesis. One isoform in particular, JNK2?, has been shown to be frequently activated in primary brain tumors, to enhance several tumorigenic phenotypes and to increase tumor formation in mice. As JNK is frequently activated in non-small cell lung carcinoma (NSCLC), we investigated the role of the JNK2? isoform in NSCLC formation by examining its expression in primary tumors and by modulating its expression in cultured cell lines. We discovered that 60% of the tested primary NSCLC tumors had three-fold higher JNK2 protein and two- to three-fold higher JNK2? mRNA expression than normal lung control tissue. To determine the importance of JNK2? in NSCLC progression, we reduced JNK2? expression in multiple NSCLC cell lines using short hairpin RNA. Cell lines deficient in JNK2? had decreased cellular growth and anchorage-independent growth, and the tumors were four-fold smaller in mass. To elucidate the mechanism by which JNK2? induces NSCLC growth, we analyzed the JNK substrate, signal transducer and activator of transcription 3 (STAT3). Our data demonstrates for the first time that JNK2? can regulate the transcriptional activity of STAT3 by phosphorylating the Ser727 residue, thereby regulating the expression of oncogenic genes, such as c-Myc. Furthermore, reintroduction of JNK2?2 or STAT3 restored the tumorigenicity of the NSCLC cells, demonstrating that JNK2? is important for NSCLC progression. Our studies reveal a novel mechanism in which phosphorylation of STAT3 is mediated by a constitutively active JNK2 isoform, JNK2?.

    View details for DOI 10.1038/onc.2010.414

    View details for Web of Science ID 000286438900011

    View details for PubMedID 20871632

  • Development of an EGFRvIII specific recombinant antibody BMC BIOTECHNOLOGY Gupta, P., Han, S., Holgado-Madruga, M., Mitra, S. S., Li, G., Nitta, R. T., Wong, A. J. 2010; 10

    Abstract

    EGF receptor variant III (EGFRvIII) is the most common variant of the EGF receptor observed in human tumors. It results from the in frame deletion of exons 2-7 and the generation of a novel glycine residue at the junction of exons 1 and 8. This novel juxtaposition of amino acids within the extra-cellular domain of the EGF receptor creates a tumor specific and immunogenic epitope. EGFRvIII expression has been seen in many tumor types including glioblastoma multiforme (GBM), breast adenocarcinoma, non-small cell lung carcinoma, ovarian adenocarcinoma and prostate cancer, but has been rarely observed in normal tissue. Because this variant is tumor specific and highly immunogenic, it can be used for both a diagnostic marker as well as a target for immunotherapy. Unfortunately many of the monoclonal and polyclonal antibodies directed against EGFRvIII have cross reactivity to wild type EGFR or other non-specific proteins. Furthermore, a monoclonal antibody to EGFRvIII is not readily available to the scientific community.In this study, we have developed a recombinant antibody that is specific for EGFRvIII, has little cross reactivity for the wild type receptor, and which can be easily produced. We initially designed a recombinant antibody with two anti-EGFRvIII single chain Fv's linked together and a human IgG1 Fc component. To enhance the specificity of this antibody for EGFRvIII, we mutated tyrosine H59 of the CDRH2 domain and tyrosine H105 of the CDRH3 domain to phenylalanine for both the anti-EGFRvIII sequence inserts. This mutated recombinant antibody, called RAb(DMvIII), specifically detects EGFRvIII expression in EGFRvIII expressing cell lines as well as in EGFRvIII expressing GBM primary tissue by western blot, immunohistochemistry (IHC) and immunofluorescence (IF) and FACS analysis. It does not recognize wild type EGFR in any of these assays. The affinity of this antibody for EGFRvIII peptide is 1.7 × 10? M?¹ as determined by enzyme-linked immunosorbent assay (ELISA).This recombinant antibody thus holds great potential to be used as a research reagent and diagnostic tool in research laboratories and clinics because of its high quality, easy viability and unique versatility. This antibody is also a strong candidate to be investigated for further in vivo therapeutic studies.

    View details for DOI 10.1186/1472-6750-10-72

    View details for Web of Science ID 000283354200001

    View details for PubMedID 20925961

  • Pineal Parenchymal Tumor of Intermediate Differentiation: Clinicopathological Report and Analysis of Epidermal Growth Factor Receptor Variant III Expression NEUROSURGERY Li, G., Mitra, S., Karamchandani, J., Edwards, M. S., Wong, A. J. 2010; 66 (5): 963-968

    Abstract

    Epidermal growth factor receptor (EGF) receptor gene amplification is commonly seen in cancer and is the target of many therapies. EGF receptor variant III (EGFRvIII) is the most common variant of the EGF receptor and has been detected in a large percentage of patients with glioblastoma multiforme but not in normal brain. Therapies targeting EGFRvIII are currently being investigated in clinical and preclinical trials.A 14-year-old girl who presented with headaches was found to have a pineal parenchymal tumor of intermediate differentiation. We review the histopathological properties that led to the diagnosis of this tumor. EGF receptor gene amplification and EGFRvIII expression have not been analyzed in pineal tumors. We investigated EGF receptor gene status and EGFRvIII expression in this patient's tumor.Tumor tissue was obtained and analyzed with flow cytometry, reverse-transcriptase polymerase chain reaction, and Western blot analysis. EGFRvIII was detected by all 3 methods. The tumor was further analyzed by fluorescence in situ hybridization, which did not reveal EGF receptor gene amplification.This is the first report of EGFRvIII expression in a pineal tumor. It is interesting that this variant is detected in the absence of EGF receptor gene amplification. A larger study evaluating the presence of EGFRvIII in pineal tumors is needed.

    View details for DOI 10.1227/01.NEU.0000367726.49003.F1

    View details for Web of Science ID 000276970800026

    View details for PubMedID 20404701

  • Passive Antibody-Mediated Immunotherapy for the Treatment of Malignant Gliomas NEUROSURGERY CLINICS OF NORTH AMERICA Mitra, S., Li, G., Harsh, G. R. 2010; 21 (1): 67-?

    Abstract

    Despite advances in understanding the molecular mechanisms of brain cancer, the outcome of patients with malignant gliomas treated according to the current standard of care remains poor. Novel therapies are needed, and immunotherapy has emerged with great promise. The diffuse infiltration of malignant gliomas is a major challenge to effective treatment; immunotherapy has the advantage of accessing the entire brain with specificity for tumor cells. Therapeutic immune approaches include cytokine therapy, passive immunotherapy, and active immunotherapy. Cytokine therapy involves the administration of immunomodulatory cytokines to activate the immune system. Active immunotherapy is the generation or augmentation of an immune response, typically by vaccination against tumor antigens. Passive immunotherapy connotes either adoptive therapy, in which tumor-specific immune cells are expanded ex vivo and reintroduced into the patient, or passive antibody-mediated therapy. In this article, the authors discuss the preclinical and clinical studies that have used passive antibody-mediated immunotherapy, otherwise known as serotherapy, for the treatment of malignant gliomas.

    View details for DOI 10.1016/j.nec.2009.08.010

    View details for Web of Science ID 000278059500007

    View details for PubMedID 19944967

  • The Epidermal Growth Factor Variant III Peptide Vaccine for Treatment of Malignant Gliomas NEUROSURGERY CLINICS OF NORTH AMERICA Li, G., Mitra, S., Wong, A. J. 2010; 21 (1): 87-?

    Abstract

    Epidermal growth factor variant III (EGFRvIII) is the most common alteration of the epidermal growth factor (EGF) receptor found in human tumors. It is commonly expressed in glioblastoma multiforme (GBM), where it was initially identified. This constitutively active mutant receptor leads to unregulated growth, survival, invasion, and angiogenesis in cells that express it. EGFRvIII results from an in-frame deletion of exons 2 to 7 resulting in the fusion of exon 1 to exon 8 of the EGF receptor gene creating a novel glycine at the junction in the extracellular amino terminal domain. The juxtaposition of ordinarily distant amino acids in combination with the glycine that forms at the junction leads to a novel tumor-specific epitope that would make an ideal tumor-specific target. A peptide derived from the EGFRvIII junction can be used as a vaccine to prevent or induce the regression of tumors. This peptide vaccine has now proceeded to phase 1 and 2 clinical trials where it has been highly successful and is now undergoing investigation in a larger human clinical trial for patients who have newly diagnosed GBM. In this article, the authors discuss the preclinical data that led to the human trials and the exciting preliminary data from the clinical trials.

    View details for DOI 10.1016/j.nec.2009.08.004

    View details for Web of Science ID 000278059500009

    View details for PubMedID 19944969

Conference Proceedings


  • COMPARISON OF DIPG NEUROSPHERE CELL LINES FROM THREE PATIENTS Monje, M., Mitra, S. S., Freret, M. E., Edwards, M. S., Weissman, I. L., Beachy, P. A. OXFORD UNIV PRESS INC. 2011: 165-165

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