Metastatic, hormone refractory prostate cancer is an incurable disease that kills over 40,000 men per year in the United States. No currently available therapy can extend life, underscoring the need for novel treatment regimens. This proposal is designed to test the hypothesis that immune manipulation can lead to prostatic infiltration with specific T cells and to regression of prostate tumors in a clinically relevant murine model. In addition, this proposal is intended to provide the principal investigator, Dr. Charles G. Drake, with the necessary training to transition from medical oncology fellow to independent clinician-scientist in the field of tumor immunology. Dr. Drake received an M.D. and Ph.D. under the auspices of the medical scientist training program (MSTP) at National Jewish Center for Immunology. His Ph.D. research involved the basic genetics and immunology of a murine model of systemic lupus erythematosus. After completing a residency in Internal Medicine on the Osler Medical Service at Johns Hopkins Hospital, Dr. Drake began clinical subspecialty training in Medical Oncology. Dr. Drake's career goal is to head an independent, laboratory-based research effort in tumor immunology with a focus on clinically relevant immunotherapeutic approaches. The training program described here will be mentored by Dr. Drew Pardoll, who has a proven track record in the field of tumor immunology in addition to a strong history of transitioning clinical fellows to independent research careers. Finally, the research and training program outlined in this proposal makes full use of the collaborative and educational opportunities offered by the Johns Hopkins Oncology Center, where this work will be performed.
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| Drake, Charles G (2015) Combined Immune Checkpoint Blockade. Semin Oncol 42:656-62 |
| Getnet, Derese; Grosso, Joseph F; Goldberg, Monica V et al. (2010) A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells. Mol Immunol 47:1595-600 |
| Wada, Satoshi; Yoshimura, Kiyoshi; Hipkiss, Edward L et al. (2009) Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model. Cancer Res 69:4309-18 |
| Yen, Hung-Rong; Harris, Timothy J; Wada, Satoshi et al. (2009) Tc17 CD8 T cells: functional plasticity and subset diversity. J Immunol 183:7161-8 |
| Sfanos, Karen S; Bruno, Tullia C; Meeker, Alan K et al. (2009) Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+. Prostate 69:1694-703 |
| Getnet, Derese; Maris, Charles H; Hipkiss, Edward L et al. (2009) Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells. J Immunol 182:4675-85 |
| Grosso, Joseph F; Goldberg, Monica V; Getnet, Derese et al. (2009) Functionally distinct LAG-3 and PD-1 subsets on activated and chronically stimulated CD8 T cells. J Immunol 182:6659-69 |
| Harris, Timothy J; Hipkiss, Edward L; Borzillary, Scott et al. (2008) Radiotherapy augments the immune response to prostate cancer in a time-dependent manner. Prostate 68:1319-29 |
| Grosso, Joseph F; Kelleher, Cristin C; Harris, Timothy J et al. (2007) LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. J Clin Invest 117:3383-92 |
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