Department of Medicine, Memorial Sloan-Kettering Cancer Center, NY 10065, USA.
Cancer J. 2011 Sep-Oct;17(5):372-8. doi: 10.1097/PPO.0b013e31823261db.
Despite significant scientific knowledge in the field of cancer immunology, therapeutic strategies using cancer vaccines to generate anti-tumor immunity have historically resulted in only modest clinical benefit. Disappointing results from prior cancer vaccine trials are likely due to multifactorial causes. Perhaps the most important is the role of inherent tumor-induced immune suppression and enhanced immunologic tolerance. Current research directed toward understanding the mechanisms of immunologic tolerance has led to the development of promising therapeutic immune regulatory antibodies that inhibit immunologic checkpoints and subsequently enhance immunologic anti-tumor activity. This review discusses the prior challenges associated with cancer vaccines and describes how, by breaking immune inhibition and facilitating immune stimulation, immune regulatory antibodies show great promise in the treatment of a variety of tumors.
尽管在癌症免疫学领域有大量的科学知识,但利用癌症疫苗产生抗肿瘤免疫的治疗策略在历史上仅产生了适度的临床获益。先前癌症疫苗试验的令人失望结果可能是由于多种因素造成的。也许最重要的是内在的肿瘤诱导免疫抑制和增强的免疫耐受作用。目前针对理解免疫耐受机制的研究导致了有前途的治疗性免疫调节抗体的开发,这些抗体抑制免疫检查点,从而增强免疫抗肿瘤活性。本文讨论了与癌症疫苗相关的先前挑战,并描述了如何通过打破免疫抑制和促进免疫刺激,免疫调节抗体在治疗各种肿瘤方面显示出巨大的潜力。