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重新利用食品和药物管理局批准的药物以促进抗肿瘤免疫。

Repurposing Food and Drug Administration-Approved Drugs to Promote Antitumor Immunity.

机构信息

Department of Hematology and Medical Oncology and Winship Cancer Institute.

Department of Microbiology and Immunology and Emory Vaccine Center, and.

出版信息

Cancer J. 2019 Mar/Apr;25(2):88-99. doi: 10.1097/PPO.0000000000000368.

Abstract

There has been a major resurgence of interest in immune-based approaches to treat cancer, based largely on the success of checkpoint inhibitors (anti-cytotoxic T-lymphocyte-associated antigen 4, anti-programmed cell death 1, and anti-programmed cell death ligand 1 antibodies) in several malignancies. However, not all tumors respond to checkpoint therapy, and there is clearly a need for additional approaches for enhancing tumor immunity. We summarize the critical elements necessary for mounting an efficacious T-cell response to a tumor. We cite drugs approved by the Food and Drug Administration for no-cancer indications that could be repurposed and used as part of an antitumor immune cocktail. We also list cancer drugs not initially intended to impact tumor immunity (soft repurposing) but that have been found to modulate the immune system. We highlight those drugs that might be used in combination with checkpoint inhibitors to increase response rates and survival of cancer patients. Our focus will be on drugs for which there are limited but existing human data. We cite supporting mechanistic mouse data as well. Repurposing drugs to modulate antitumor immunity is an opportunity to rapidly bring new, effective, and affordable treatments to cancer patients.

摘要

基于检查点抑制剂(抗细胞毒性 T 淋巴细胞相关抗原 4、抗程序性细胞死亡 1 和抗程序性细胞死亡配体 1 抗体)在多种恶性肿瘤中的成功,免疫治疗癌症的方法再次受到广泛关注。然而,并非所有肿瘤对检查点治疗都有反应,显然需要额外的方法来增强肿瘤免疫。我们总结了引发针对肿瘤的有效 T 细胞反应所需的关键要素。我们列举了已获美国食品和药物管理局批准用于非癌症适应症的药物,这些药物可重新用于作为抗肿瘤免疫鸡尾酒的一部分。我们还列出了最初并非旨在影响肿瘤免疫的癌症药物(软性重新定位),但已被发现可调节免疫系统。我们重点介绍那些可能与检查点抑制剂联合使用以提高癌症患者的反应率和生存率的药物。我们的重点将放在那些药物上,这些药物在人类中的数据有限但存在。我们也引用了支持的机制学小鼠数据。将药物重新用于调节抗肿瘤免疫是为癌症患者带来新的、有效且负担得起的治疗方法的机会。

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