The broad, long-term objectives of our research are: i) to develop and optimize dendritic cell-based immunotherapy approaches for the treatment of brain tumors;and ii) to gain a better understanding of the mechanisms of immune responses generated by dendritic cell-based strategies targeting central nervous system (CMS) neoplasms. To do this, we propose three specific aims designed to understand, both in pre-clinical animal models as well as in clinical patient samples, the mechanisms of anti-tumor immunity critical for CMS tumor eradication. Immunotherapy for glioma has traditionally lagged behind other peripheral tumors where defined CTL targets are known. In our recent pre-clinical studies we have shown that both human and murine gliomas express melanoma-associated antigens (MAA)that can be recognized by the cellular immune system. We believe that the shared expression of MAA on gliomas and melanomas stems from their common neuroectodermal origin. Our discovery was important because it identified a set of endogenous tumor-associated antigens (TAA) on gliomas that have well characterized cytotoxic T lymphocyte (CTL) epitopes. Using our T cell receptor transgenic mouse model, in vivo imaging methodologies, and Toll-like receptor (TLR) agonists, we have designed a systematic set of studies to not only test the therapeutic value of targeting MAA on CMS tumors, but provide a model to test the basic immunological requirements for generating anti-tumor immunity to defined, endogenous MAA located in the CNS. Our central hypothesis is that CNS gliomas express MAA, which can be targeted by immunotherapies that enhance T cell and DC activation and trafficking. Thus, this is a mechanistic and translational project that is directly related to our long-term objectives stated above and to the mission of promoting public health.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA123396-04
Application #
7754039
Study Section
Special Emphasis Panel (ZRG1-BDCN-N (02))
Program Officer
Yovandich, Jason L
Project Start
2007-04-01
Project End
2012-07-31
Budget Start
2010-02-01
Budget End
2012-07-31
Support Year
4
Fiscal Year
2010
Total Cost
$234,840
Indirect Cost
Name
University of California Los Angeles
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Prins, Robert M; Wang, Xiaoyan; Soto, Horacio et al. (2013) Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients. J Immunother 36:152-7
Pope, Whitney B; Prins, Robert M; Albert Thomas, M et al. (2012) Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy. J Neurooncol 107:197-205
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