The choice of the antigen in the dendritic cell-based vaccine therapy for prostate cancer

Summary 

Tumor antigens (TA) are promising candidates for targeted treatment of prostate cancer (PCa). Critical issues in the preparation of dendritic cell (DC)-based TA vaccines are the DC maturation state and the appropriateness of the TA. Prostate-specific antigen (PSA) and prostate acide pshosphatase (PAP) presented by DC have produced encouraging results and PAP-loaded DCs are at late-stage development for PCa patients. TAs indispensable for tumor survival and propagation are now emerging as first choice TAs for future vaccines. The increased expression and enzymatic activity of prostate specific membrane antigen (PSMA) and prostate stem cell antigen (PSCA) by aggressive prostate tumors is indicative of a unique, selective advantage on the part of cells expressing them. Human telomerase reverse transcriptase (hTERT) and survivin are both involved in tumor cell survival and considered universal TAs. The T cell epitope potential of peptides derived from these TAs has been defined by computer-assisted prediction programs and has been tested in vitro and in vivo in terms of their ability to recruit cytotoxic T lymphocytes (CTL) and to be recognised as CTL targets. Results, reviewed here, show that anti-tumor immunity can be induced in vivo by DC loaded with both whole TAs and TA peptides. The promising, but still limited clinical success suggests further exploration of this immune therapy in the more appropriate setting of minimal disease. In advanced stages, vaccine can still be effective when combined with systemic or local cytoreductive therapies, which may overcome antigen specific tolerance and subvert the tumor immunosuppressive environment.

Abbreviations: TA, tumor antigen, PCa, prostate cancer, PSMA, prostate specific membrane antigen, PSCA, prostate stem cell antigen, hTERT, human telomerase reverse transcriptase, CTL, cytotoxic T lymphocytes, DC, dendritic cell, iDC, immature dendritic cell, mDC, mature dendritic cell, PSA, prostate-specific antigen, PAP, prostatic acid phosphatase, STEAP, six-transmembrane epithelial antigen of the prostate, PIN, prostatic intraepithelial neoplasia, BPH, benign prostatic hyperplasia

Keywords: Prostate cancer, Tumor-associated antigens, Vaccine, Dendritic cells, PSA, PAP, PSMA, PSCA, hTERT, Survivin