Vonderheide Robert H
Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Discov Med. 2007 Aug;7(39):103-8.
Despite their much-heralded clinical potential, therapeutic cancer vaccines have thus far failed to achieve the necessary clinical benchmarks to allow their regulatory approval. In contrast, vaccination against infectious pathogens represents one of the biggest achievements of modern medicine, and in certain cases such as vaccines against the human papilloma virus or hepatitis B virus, vaccination may impact the development of cancer. To the extent that these two approaches differ as immunotherapy vs. immunoprevention, the challenge is to rethink the types of non-viral antigens that are currently being targeted in cancer vaccines. Immunological analysis suggests that the telomerase reverse transcriptase hTERT is a widely applicable target recognized by T lymphocytes and a prototype for a novel class of universal tumor antigens. Findings from initial clinical trials demonstrate that hTERT-specific immune responses can be safely induced in cancer patients. If the amplitude and duration of cellular immunity against hTERT can be optimized without toxicity in humans, then an opportunity exists to test hTERT vaccination as a way to reduce the risk of cancer recurrence in patients or even the risk of developing cancer in otherwise healthy individuals.
尽管治疗性癌症疫苗具有备受瞩目的临床潜力，但迄今为止，它们尚未达到获得监管批准所需的临床标准。相比之下，针对传染性病原体的疫苗接种是现代医学的最大成就之一，在某些情况下，如针对人乳头瘤病毒或乙型肝炎病毒的疫苗，疫苗接种可能会影响癌症的发展。就这两种方法在免疫治疗与免疫预防方面的差异而言，挑战在于重新思考目前癌症疫苗所针对的非病毒抗原类型。免疫学分析表明，端粒酶逆转录酶hTERT是一种被T淋巴细胞广泛识别的适用靶点，也是一类新型通用肿瘤抗原的原型。初步临床试验结果表明，在癌症患者中可以安全地诱导出针对hTERT的免疫反应。如果针对hTERT的细胞免疫的幅度和持续时间能够在无毒性的情况下在人体中得到优化，那么就有机会测试hTERT疫苗接种，作为降低患者癌症复发风险甚至降低健康个体患癌风险的一种方法。
