Enhancing Therapeutic Cellular Prostate Cancer Vaccines

Abstract : Prostate cancer (CaP) remains among the most common causes of cancer related deaths in men. Because CaP is characterized by unique prostate associated antigens, it has been considered among prime candidates for immunotherapy. Despite numerous laboratory advances, clinical outcomes have been partial and transient. One plausible reason for the incomplete response is that vaccine cells, prepared under standard tissue culture conditions, can drastically differ in expression of macromolecules in situ, and thus may immunize against a less complete antigen spectrum. The purpose of the proposed studies is to optimize the effectiveness of therapeutic whole cell CaP vaccines by taking into consideration tumor associated hypoxia as a relevant determinant factor of tumor antigenicity. We hypothesize that hypoxically cultured CaP cells are more similar in their antigen landscape to CaP cells in situ than are normoxically cultured CaP cells. The following Tasks were defined in the approved statement of work; Task 1. Identify oxygen tension responsive genes and proteins in the cells comprising a clinical grade CaP cellular vaccine. This first task was accomplished at the end of the first period. Task 2. Validate differentially expressed molecules in CaP that are associated with tissue hypoxia. This last task has been partially executed and is reported in the present progress report. If the proposed studies demonstrate that CaP cells grown under low oxygen tension (pO2) are more antigenically similar to cells in situ, this will justify the evaluation of their therapeutic value in a preclinical model.