Immunotherapy represents a promising approach to prostate cancer treatment. Recent data from our laboratory (as well as others) shows that the immune checkpoint mediated by interactions between the T cell surface molecule known as PD-1 and the molecule B7-H1 on cancer cells can inhibit an anti-tumor immune response. Thus, blockade of this interaction using monoclonal antibodies directed against PD-1 may play a role in prostate cancer treatment. Our group has also shown that anti-cancer vaccines based on attenuated Listeria Monocytogenes (LM) show a striking synergy with blockade of the PD-1 / B7-H1 checkpoint. Thus, we propose a Phase I trial combining these two agents for men with prostate cancer. Because disease burden plays a major role in the outcome of immunotherapy, we have chosen to target men with minimal disease, i.e. men who have undergone radiation therapy for high-risk disease. Both of the agents employed here are currently in Phase I testing, and those data will be used to fine-tune the combinatorial approach. The trial includes several critical immune correlates to test the central hypothesis that the combination of PD-1 blockade and PSCA-specific LM-based vaccination will

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
3P50CA058236-18S1
Application #
8719551
Study Section
Special Emphasis Panel (ZCA1-RPRB-M)
Project Start
2013-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
18
Fiscal Year
2013
Total Cost
$159,142
Indirect Cost
$60,906
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Regter, Sietze; Hedayati, Mohammad; Zhang, Yonggang et al. (2014) Androgen withdrawal fails to induce detectable tissue hypoxia in the rat prostate. Prostate 74:805-10
Ku, ShengYu; Lasorsa, Elena; Adelaiye, Remi et al. (2014) Inhibition of Hsp90 augments docetaxel therapy in castrate resistant prostate cancer. PLoS One 9:e103680
Chalfin, Heather J; Frank, Steven M; Feng, Zhaoyong et al. (2014) Allogeneic versus autologous blood transfusion and survival after radical prostatectomy. Transfusion 54:2168-74
Bhatnagar, Akrita; Wang, Yuchuan; Mease, Ronnie C et al. (2014) AEG-1 promoter-mediated imaging of prostate cancer. Cancer Res 74:5772-81
Brennen, W Nathaniel; Rosen, D Marc; Chaux, Alcides et al. (2014) Pharmacokinetics and toxicology of a fibroblast activation protein (FAP)-activated prodrug in murine xenograft models of human cancer. Prostate 74:1308-19
Paller, C J; Olatoye, D; Xie, S et al. (2014) The effect of the frequency and duration of PSA measurement on PSA doubling time calculations in men with biochemically recurrent prostate cancer. Prostate Cancer Prostatic Dis 17:28-33
Durham, Nicholas M; Nirschl, Christopher J; Jackson, Christopher M et al. (2014) Lymphocyte Activation Gene 3 (LAG-3) modulates the ability of CD4 T-cells to be suppressed in vivo. PLoS One 9:e109080
Gurel, Bora; Lucia, M Scott; Thompson Jr, Ian M et al. (2014) Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev 23:847-56
Lutz, Eric R; Wu, Annie A; Bigelow, Elaine et al. (2014) Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation. Cancer Immunol Res 2:616-31
Zheng, Qizhi; Peskoe, Sarah B; Ribas, Judit et al. (2014) Investigation of miR-21, miR-141, and miR-221 expression levels in prostate adenocarcinoma for associated risk of recurrence after radical prostatectomy. Prostate 74:1655-62

Showing the most recent 10 out of 579 publications