Malignant gliomas represent a significant class of CNS tumors derived from the glial lineage. Despite recent advances in traditional treatment options, the prognosis for these patients has not changed appreciably. Among the new treatments currently being investigated for malignant cancers, none is as theoretically appealing as immunotherapy because it offers the potential for high tumor-specific toxicity. Immune-based treatments for central nervous system (CNS) gliomas have traditionally lagged behind those of more immunogenic tumors such as melanoma. The relative paucity of defined glioma-associated antigens (GAA) that can be targeted by the immune system may partially account for this situation. Antigens present on melanomas have been extensively characterized, both in humans and murine pre-clinical models. Melanocytes and astrocytes are both derived embryologically from the neural ectoderm. Their neoplastic counterparts, malignant melanomas and gliomas, have been shown in humans to share common antigens at the RNA level. However, little is known concerning whether gliomas can be targeted by immune-based strategics that prime T cells to epitopes from melanoma-associated antigens (MAA). The experiments outlined in this proposal are primarily designed to test whether MAA are expressed by gliomas and recognized by the immune system. This proposal will also define the basic immunologic requirements for targeting tumors located within the CNS. The results from this study should not only provide important basic immunologic data concerning T lymphocyte responses in the CNS, but could potentially outline a new immunotherapeutic target for CNS tumors clinically. The tumor immunology program and academic environment at UCLA offers an ideal place to develop as an independent research scientist. World renowned scientists and technology in many disciplines will serve to enhance the ability of Dr. Prins to accomplish the goals set forth in this application.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01CA111402-05
Application #
7842484
Study Section
Subcommittee G - Education (NCI)
Program Officer
Lohrey, Nancy
Project Start
2006-07-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2012-06-30
Support Year
5
Fiscal Year
2010
Total Cost
$148,770
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
Everson, Richard G; Antonios, Joseph P; Lisiero, Dominique N et al. (2016) Efficacy of systemic adoptive transfer immunotherapy targeting NY-ESO-1 for glioblastoma. Neuro Oncol 18:368-78
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
Fong, Brendan; Jin, Richard; Wang, Xiaoyan et al. (2012) Monitoring of regulatory T cell frequencies and expression of CTLA-4 on T cells, before and after DC vaccination, can predict survival in GBM patients. PLoS One 7:e32614
Prins, Robert M; Soto, Horacio; Konkankit, Vera et al. (2011) Gene expression profile correlates with T-cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy. Clin Cancer Res 17:1603-15
Lisiero, Dominique N; Soto, Horacio; Liau, Linda M et al. (2011) Enhanced sensitivity to IL-2 signaling regulates the clinical responsiveness of IL-12-primed CD8(+) T cells in a melanoma model. J Immunol 186:5068-77
Konkankit, Veerauo V; Kim, Won; Koya, Richard C et al. (2011) Decitabine immunosensitizes human gliomas to NY-ESO-1 specific T lymphocyte targeting through the Fas/Fas ligand pathway. J Transl Med 9:192
Hickey, Michelle J; Malone, Colin C; Erickson, Kate L et al. (2010) Cellular and vaccine therapeutic approaches for gliomas. J Transl Med 8:100
Prins, Robert M; Shu, Chengyi J; Radu, Caius G et al. (2008) Anti-tumor activity and trafficking of self, tumor-specific T cells against tumors located in the brain. Cancer Immunol Immunother 57:1279-89
Prins, Robert M; Cloughesy, Timothy F; Liau, Linda M (2008) Cytomegalovirus immunity after vaccination with autologous glioblastoma lysate. N Engl J Med 359:539-41

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