title: Clinical evaluation of TRICOM vector therapeutic cancer vaccines.
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.
authors.affiliation: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Madan
authors.forename: Marijo
authors.initials: M
authors.lastname: Bilusic
authors.forename: Christopher
authors.initials: C
authors.lastname: Heery
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D019076:Transgenes; D014614:Vaccines, Synthetic / Q000276:immunology / Q000494:pharmacology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D014614:Vaccines, Synthetic