Enhancing Therapeutic Cellular Prostate Cancer Vaccines

Prostate cancer CaP is characterized by unique prostate-associated antigens hence, it has been considered a prime candidate for immunotherapy. Despite numerous laboratory advances, clinical outcomes have been partial and transient. The overall goal 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 of tumor antigenicity. Transcriptome studies revealed that gene expression in hypoxically cultured cells is more akin to that in tumor cells in situ than are cells grown normoxically. Transcripts of hypoxia-associated genes DLG7, CCNB1 and HMMR were associated with Gleason score and with disease prognosis suggesting their potential as CaP biomarkers with prognostic value. By 2D-gel electrophoresis, we screened patient sera and detected novel hypoxic-cell reactive autoantibodies under validation. Our data suggest that hypoxically cultured CaP cells are more akin to tumor cells in situ than are cells grown normoxically. We have identified hypoxia-reactive proteins, pathways and autoantigens with potential value as biomarkers or therapeutic targets. Introduction of pO2 as a variable can constitute a tool for the development of more effective immunotheraphy for CaP.