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免疫肿瘤药物的研发——从 CTLA4 到 PD1 再到下一代。

Development of immuno-oncology drugs - from CTLA4 to PD1 to the next generations.

机构信息

Oncology Research and Development, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA.

出版信息

Nat Rev Drug Discov. 2016 Apr;15(4):235-47. doi: 10.1038/nrd.2015.35. Epub 2016 Mar 11.

Abstract

Since the regulatory approval of ipilimumab in 2011, the field of cancer immunotherapy has been experiencing a renaissance. This success is based on progress in both preclinical and clinical science, including the development of new methods of investigation. Immuno-oncology has become a sub-specialty within oncology owing to its unique science and its potential for substantial and long-term clinical benefit. Immunotherapy agents do not directly attack the tumour but instead mobilize the immune system - this can be achieved through various approaches that utilize adaptive or innate immunity. Therefore, immuno-oncology drug development encompasses a broad range of agents, including antibodies, peptides, proteins, small molecules, adjuvants, cytokines, oncolytic viruses, bi-specific molecules and cellular therapies. This Perspective summarizes the recent history of cancer immunotherapy, including the factors that led to its success, provides an overview of novel drug-development considerations, summarizes three generations of immunotherapies that have been developed since 2011 and, thus, illustrates the breadth of opportunities these new generations of immunotherapies represent.

摘要

自 2011 年伊匹单抗获得监管批准以来,癌症免疫疗法领域正在经历复兴。这一成功基于临床前和临床科学的进展,包括新的研究方法的发展。由于其独特的科学和潜在的实质性和长期临床获益,免疫肿瘤学已成为肿瘤学的一个亚专科。免疫疗法药物不是直接攻击肿瘤,而是调动免疫系统——这可以通过利用适应性或固有免疫的各种方法来实现。因此,免疫肿瘤学药物开发涵盖了广泛的药物,包括抗体、肽、蛋白质、小分子、佐剂、细胞因子、溶瘤病毒、双特异性分子和细胞疗法。本文概述了癌症免疫疗法的近期历史,包括导致其成功的因素,概述了新型药物开发的考虑因素,总结了自 2011 年以来开发的三代免疫疗法,从而说明了这些新的免疫疗法代表了广泛的机会。

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