Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Semin Oncol. 2012 Jun;39(3):296-304. doi: 10.1053/j.seminoncol.2012.02.010.
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.
我们开发了一种“现成”的基于载体的疫苗平台，其中包含与癌相关的抗原和多个共刺激分子的转基因（称为 TRICOM）。已经在临床前和临床试验中评估了两种 TRICOM 平台。PROSTVAC 由 rV、rF-PSA-TRICOM 组成，用于前列腺癌治疗试验。PANVAC 由 rV、rF-CEA-MUC1-TRICOM 组成；两个泛癌转基因 CEA 和 MUC-1 的表达使 PANVAC 疫苗接种适用于多种人类癌的治疗应用。由于完成和正在进行的 TRICOM 疫苗试验，出现了许多新的范例，包括（1）患者受益的临床证据可能会延迟，因为可能需要多次接种以诱导足够的抗肿瘤免疫反应；（2）当 TRICOM 疫苗作为单一疗法使用时，生存而不是严格遵守 RECIST 标准或进展时间可能是最合适的试验终点；（3）与其他疗法相比，某些患者群体更有可能从疫苗治疗中受益；（4）由于疫苗的毒性有限，TRICOM 疫苗与标准治疗药物联合使用，无论是同时还是序贯使用，都是可行的。
