Lowering T Cell Activation Thresholds and Deregulating Homeostasis to Facilitate Immunotherapeutic Responses to Treat Prostate Cancer
Final rept. 1 Apr 2003-31 Mar 2006
MAYO CLINIC ROCHESTER MN
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The inductor of tumor-specific T cells remains a primary obstacle to immunotherapeutic approaches for most cancers including prostate cancer This difficulty has been largely ascribed to mechanisms for tumor evasion of the immune system and host-imposed restrictions collectively referred to as tolerance that prevent cross-reactive autoimmunity against the parent tissues from which tumors arise. Limitations in techniques to identify novel and truly immunogenic prostate-spew antigens and efficient methods to modify autologous tissues for vaccine preparation have further constrained approaches to develop immune-based therapies for prostate cancer Hence, relatively straightforward manipulations that induce specific T cell responses against prostate tumors or epithelial tissues, especially in vivo, might ultimately prove valuable for prostate cancer immunotherapy Our studies explore a new paradigm in which we will exploit blockade of T cell purigenic receptors A2a and A2b using caffeine to alleviate tumor-induced impairments in T cell function to potentiate T cell-mediated immunotherapeutic responses to treat established prostate tumors in mice.
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