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紫杉醇作为实体瘤中与检查点抑制剂联用的潜在药物。

-Paclitaxel as a potential partner with checkpoint inhibitors in solid tumors.

作者信息

Soliman Hatem H

机构信息

Department of Oncologic Sciences, Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL, USA.

出版信息

Onco Targets Ther. 2016 Dec 21;10:101-112. doi: 10.2147/OTT.S122974. eCollection 2017.

Abstract

Tumors recognized by the host immune system are associated with better survival. However, the immune system is often suppressed in patients with established tumor burden. Stimulating the immune system to detect and kill tumor cells has been a challenge in cancer therapy for some time. Recently, novel cancer immunotherapies, such as immune checkpoint inhibitors, monoclonal antibodies, and vaccine therapies, have emerged as promising therapeutic approaches for many solid tumors. However, for some tumors, immunotherapy alone has not provided significant benefits, and some may even be fully resistant to immunotherapy. It has been suggested that the immune system may require "priming" before an immunotherapy can elicit an immune response. Although chemotherapies are believed to be immunosuppressive, when given at the right dose and sequence these agents may provide this "priming" effect for the immune system. In addition to direct cytotoxic killing of tumor cells, standard chemotherapeutic agents can elicit immunogenicity through various mechanisms. This review highlights the general immunomodulatory properties of chemotherapy agents. It also provides a rationale for combined therapy with -paclitaxel and immune checkpoint inhibitors. Recent clinical trial data with these combination regimens in solid tumors are presented, along with a summary of ongoing trials.

摘要

被宿主免疫系统识别的肿瘤与更好的生存率相关。然而,在已有肿瘤负荷的患者中,免疫系统常常受到抑制。一段时间以来,刺激免疫系统检测和杀死肿瘤细胞一直是癌症治疗中的一项挑战。最近,新型癌症免疫疗法,如免疫检查点抑制剂、单克隆抗体和疫苗疗法,已成为许多实体瘤有前景的治疗方法。然而,对于某些肿瘤,单纯免疫疗法并未带来显著益处,有些甚至可能对免疫疗法完全耐药。有人提出,在免疫疗法引发免疫反应之前,免疫系统可能需要“启动”。尽管化疗被认为具有免疫抑制作用,但在给予适当剂量和顺序时,这些药物可能为免疫系统提供这种“启动”效应。除了直接对肿瘤细胞进行细胞毒性杀伤外,标准化疗药物还可通过多种机制引发免疫原性。本综述强调了化疗药物的一般免疫调节特性。它还为紫杉醇与免疫检查点抑制剂联合治疗提供了理论依据。文中呈现了这些联合方案在实体瘤中的近期临床试验数据,以及正在进行的试验总结。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f426/5189972/4653b475bcec/ott-10-101Fig1.jpg

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