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阿维鲁单抗:探索免疫检查点抑制与化疗的联合应用。

Avelumab: search for combinations of immune checkpoint inhibition with chemotherapy.

作者信息

Hamilton Gerhard

机构信息

Department of Vascular Biology, Medical University of Vienna, Vienna, Austria.

出版信息

Expert Opin Biol Ther. 2021 Mar;21(3):311-322. doi: 10.1080/14712598.2021.1825679. Epub 2020 Oct 3.

Abstract

INTRODUCTION

Immune checkpoint inhibition (ICI) has proved successful for selected tumors and a subpopulation of patients. The human monoclonal IgG1 antibody (mAB) avelumab capable of mediating antibody-dependent cytotoxicity (ADCC) lysis is directed to programmed death ligand-1 (PD-L1) of tumor cells and is tested in trials aiming to improve ICI in combination with chemotherapeutic drugs.

AREAS COVERED

This article presents an overview of the current trials to enhance ICI regimens using avelumab in combination with chemotherapeutics, antiangiogenetic drugs, and immunomodulators. Predictive factors for this kind of immunochemotherapy are discussed.

EXPERT OPINION

Clinical data demonstrate that avelumab shows efficacy in cancer patients against Merkel cell carcinoma (MCC), renal cell carcinoma (RCC), and urothelial cancers as single agent. Furthermore, avelumab in combination with axitinib in RCC increases survival and exhibits activity in combination with docetaxel in urothelial carcinoma. However, several other immunochemotherapy trials for ovarian cancer, gastric cancer, and non-small lung cancer (NSCLC) showed no activity due to factors disfavoring administration of immunotherapy combos.

摘要

引言

免疫检查点抑制(ICI)已被证明对特定肿瘤和部分患者亚群有效。人源单克隆IgG1抗体(mAB)阿维鲁单抗能够介导抗体依赖性细胞毒性(ADCC)裂解,靶向肿瘤细胞的程序性死亡配体-1(PD-L1),并在旨在将ICI与化疗药物联合以改善疗效的试验中接受测试。

涵盖领域

本文概述了目前使用阿维鲁单抗联合化疗药物、抗血管生成药物和免疫调节剂来增强ICI方案的试验情况。讨论了此类免疫化疗的预测因素。

专家观点

临床数据表明,阿维鲁单抗作为单一药物在癌症患者中对默克尔细胞癌(MCC)、肾细胞癌(RCC)和尿路上皮癌显示出疗效。此外,阿维鲁单抗与阿昔替尼联合用于RCC可提高生存率,与多西他赛联合用于尿路上皮癌也表现出活性。然而,其他几项针对卵巢癌、胃癌和非小细胞肺癌(NSCLC)的免疫化疗试验由于不利于免疫治疗联合用药的因素而未显示出活性。

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