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十二种可治愈癌症的免疫疗法药物。

Twelve immunotherapy drugs that could cure cancers.

作者信息

Cheever Martin A

机构信息

Seattle Cancer Care Alliance, Fred Hutchinson/University of Washington Cancer Consortium, Seattle, WA 98109-1023, USA.

出版信息

Immunol Rev. 2008 Apr;222:357-68. doi: 10.1111/j.1600-065X.2008.00604.x.

Abstract

Immune T cells can kill cancer cells. Cancer vaccines function by increasing the number of immune T cells. There are exceedingly strict biologic limits imposed on the immune system to prevent excessive T-cell activation and expansion. The same biological restrictions limit cancer vaccines. Immunotherapeutic agents that circumvent the biological restrictions have been invented and formulated, including (i) dendritic cell activators and growth factors, (ii) vaccine adjuvants, (iii) T-cell stimulators and growth factors, (iv) immune checkpoint inhibitors, and (v) agents to neutralize or inhibit suppressive cells, cytokines, and enzymes. Few of these agents are broadly available for the development of effective multiple component regimens. The major problem facing immunotherapy today is a lack of broad availability of agents already in existence. The National Cancer Institute has developed a well-vetted ranked list of agents with high potential to serve as immunotherapeutic drugs. This review focuses on 12 of the agents, all with proven ability to augment T-cell responses. Alone, each has little chance of making substantial inroads into cancer therapy. In combinations dictated by biology, the agents are overwhelmingly likely to have an impact. Future availability of these agents for development of innovative combination cancer therapy regimens will provide a benchmark for the resolve of the national cancer therapy translational research enterprise.

摘要

免疫T细胞能够杀死癌细胞。癌症疫苗通过增加免疫T细胞的数量发挥作用。免疫系统受到极其严格的生物学限制,以防止T细胞过度激活和扩增。同样的生物学限制也制约着癌症疫苗。人们已经发明并配制出了规避这些生物学限制的免疫治疗药物,包括:(i)树突状细胞激活剂和生长因子;(ii)疫苗佐剂;(iii)T细胞刺激剂和生长因子;(iv)免疫检查点抑制剂;以及(v)中和或抑制抑制性细胞、细胞因子和酶的药物。这些药物中很少有能广泛用于开发有效的多组分治疗方案的。当今免疫治疗面临的主要问题是现有药物缺乏广泛的可及性。美国国立癌症研究所已经制定了一份经过充分审查的、具有很高潜力可作为免疫治疗药物的药物排名清单。本综述聚焦于其中12种药物,所有这些药物都已被证明有增强T细胞反应的能力。单独使用时,它们中任何一种都几乎没有机会在癌症治疗中取得重大进展。按照生物学规律进行组合时,这些药物极有可能产生影响。这些药物未来用于开发创新型联合癌症治疗方案的可及性,将为国家癌症治疗转化研究事业的决心提供一个基准。

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