Abstract
We have developed an "off-the-shelf" vector-based vaccine platform containing transgenes for carcinoma-associated antigens and multiple costimulatory molecules (designated TRICOM). Two TRICOM platforms have been evaluated both preclinically and in clinical trials. PROSTVAC consists of rV, rF-PSA-TRICOM and is being used in prostate cancer therapy trials. PANVAC consists of rV, rF-CEA-MUC1-TRICOM; the expression of the two pan-carcinoma transgenes CEA and MUC-1 renders PANVAC vaccination applicable for therapeutic applications for a range of human carcinomas. Many new paradigms have emerged as a consequence of completed and ongoing TRICOM vaccine trials, including (1) clinical evidence of patient benefit may be delayed, because multiple vaccinations may be necessary to induce a sufficient anti-tumor immune response; (2) survival, and not strict adherence to RECIST criteria or time-to-progression, may be the most appropriate trial endpoint when TRICOM vaccines are used as monotherapy; (3) certain patient populations are more likely to benefit from vaccine therapy as compared to other therapeutics; and (4) TRICOM vaccines combined with standard-of-care therapeutics, either concomitantly or sequentially, are feasible because of the limited toxicity of vaccines.