Cancer Immunotherapy Comes of Age
Cancer Immunotherapy Comes of Age
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DOI：
10.1200/jco.2011.38.0899
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发表时间：
2011-12-20
影响因子：
45.3
通讯作者：
Pardoll, Drew M.
中科院分区：
文献类型：
--
作者：
Topalian, Suzanne L.;Weiner, George J.;Pardoll, Drew M.
癌症免疫疗法包括多种治疗方法，结合了适应性免疫系统（T细胞和抗体）的巨大特异性以及适应性和先天免疫的多样和有效的细胞毒性武器。免疫治疗策略包括抗肿瘤单克隆抗体、癌症疫苗、过继转移离体活化T细胞和自然杀伤细胞，以及施用共刺激免疫细胞或阻断免疫抑制途径（所谓的免疫检查点）的抗体或重组蛋白。尽管自20世纪90年代末以来，抗肿瘤抗体已证明了明确的临床疗效，但直到最近，当一系列成功确立了这种治疗方式的广泛潜力时，其他免疫疗法才被证明有效。这些成功是基于基础科学进展，证明了癌症的耐受性和肿瘤免疫微环境在抑制抗肿瘤免疫中的关键作用。基于免疫抑制细胞、可溶性因子和信号通路的复杂知识的新疗法旨在打破耐受性并重新激活抗肿瘤免疫，以诱导有效、持久的反应。临床前模型表明了复杂的综合免疫应答在消除已建立的肿瘤中的重要性，并验证了对组合治疗方案的探索，预计组合治疗方案比单一疗法有效得多。与传统的癌症疗法不同，大多数免疫疗法是主动和动态的，能够诱导免疫记忆，以传播肿瘤和宿主之间平衡的成功再平衡。J Clin Oncol 29：4828-4836. (C)2011年美国临床肿瘤学会
Cancer immunotherapy comprises a variety of treatment approaches, incorporating the tremendous specificity of the adaptive immune system (T cells and antibodies) as well as the diverse and potent cytotoxic weaponry of both adaptive and innate immunity. Immunotherapy strategies include antitumor monoclonal antibodies, cancer vaccines, adoptive transfer of ex vivo activated T and natural killer cells, and administration of antibodies or recombinant proteins that either costimulate immune cells or block immune inhibitory pathways (so-called immune checkpoints). Although clear clinical efficacy has been demonstrated with antitumor antibodies since the late 1990s, other immunotherapies had not been shown to be effective until recently, when a spate of successes established the broad potential of this therapeutic modality. These successes are based on fundamental scientific advances demonstrating the toleragenic nature of cancer and the pivotal role of the tumor immune microenvironment in suppressing antitumor immunity. New therapies based on a sophisticated knowledge of immune-suppressive cells, soluble factors, and signaling pathways are designed to break tolerance and reactivate antitumor immunity to induce potent, long-lasting responses. Preclinical models indicate the importance of a complex integrated immune response in eliminating established tumors and validate the exploration of combinatorial treatment regimens, which are anticipated to be far more effective than monotherapies. Unlike conventional cancer therapies, most immunotherapies are active and dynamic, capable of inducing immune memory to propagate a successful rebalancing of the equilibrium between tumor and host. J Clin Oncol 29: 4828-4836. (C) 2011 by American Society of Clinical Oncology