CDK5 A Novel Role in Prostate Cancer Immunotherapy
Technical Report,30 Sep 2015,29 Sep 2016
JOHNS HOPKINS UNIV BALTIMORE MD 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 depletion of CD4 and CD8 T cells resulted in more rapid tumor growth, and significant shortening of survival of mice in the TRAMP prostate cancer model with a prostate specific Cdk5 gene knockout. The significance of this finding is that it functionally establishes Cdk5 as an important mediator of antitumor immune response in prostate cancer. This opens the potential for a promising therapeutic strategy using a CDK inhibitor to sensitize prostate cancer to immunotherapy.
- Medicine and Medical Research