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CDK5-A Novel Role in Prostate Cancer Immunotherapy
Technical Report,30 Sep 2016,29 Sep 2017
Johns Hopkins University Baltimore United States
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Our project will establish the role of CDK5 in promoting the immunosuppressive microenvironment in prostate cancer, and identify optimal strategies for incorporation of CDK5 inhibition to augment the efficacy of immunotherapy for prostate cancer. We will confirm our observation of the involvement of a T cell antitumor response in impaired growth of prostate cancer in immunocompetent murine models of prostate cancer, and characterize the changes induced in immune cells in the tumors. Preclinical translational studies, employing a CDK5 inhibitor in combination with immunotherapies, including immune checkpoint blockers, a prostate cancer vaccine, and other agents will be conducted and optimized in vivo in an immunocompetent prostate cancer model. If successful, these therapeutic strategies can be rapidly advanced to clinical evaluation. In this reporting period, our most significant finding was that Cdk5 gene silencing by shRNA in the TRAMP-C2 prostate cancer cell line sensitized allografts to combined immune checkpoint blockade, using anti-CTLA4 and anti-PD-1 antibodies. The significance of this finding is that it provides a promising potential therapeutic strategy for prostate cancer, using a combination of CDK5 inhibition and immune checkpoint blockade.
APPROVED FOR PUBLIC RELEASE