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三阴性乳腺癌治疗的新免疫靶点。

Novel immune targets for the treatment of triple-negative breast cancer.

机构信息

Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, Irccs, Milan, Italy.

Department of Oncology and Hematology (DIPO), University of Milano, Milano, Italy.

出版信息

Expert Opin Ther Targets. 2021 Oct;25(10):815-834. doi: 10.1080/14728222.2021.2006187. Epub 2021 Nov 25.

Abstract

INTRODUCTION

To overcome mechanisms of primary and secondary resistance to the anti-tumor immune response, novel targets such as ICOS, LAG3, and TIM3 are currently being explored at preclinical and early-phase clinical levels.

AREAS COVERED

This article examines the landscape of the immune therapeutics investigated in early-phase clinical trials for TNBC. Preclinical rationale is provided for each immune target, predominant expression, and function. Clinical implications and preliminary available trial results are discussed and finally, we reflect on aspects of future expectations and challenges in this field.

EXPERT OPINION

Several immune strategies have been investigated in TNBC, including co-inhibitory molecules beyond PD1-PD-L1 axis, co-stimulatory checkpoints, cancer vaccines, adoptive cell transfer, combination therapies, as well as different routes of administration. Most of approaches showed signs of anti-cancer activity and a good safety profile in early-phase clinical trials. Since IO provided benefit only to a small subgroup of TNBC patients so far, identifying predictive biomarkers is a priority to refine patient-selection. Data from ongoing clinical trials, with the gradually improving interpretation of the breast tumor immune environment, will hopefully refine the role of new immune targets for the treatment of TNBC.

摘要

简介

为了克服抗肿瘤免疫反应的原发性和继发性耐药机制,目前正在临床前和早期临床阶段探索新型靶点,如 ICOS、LAG3 和 TIM3。

涵盖领域

本文研究了早期临床试验中用于三阴性乳腺癌的免疫治疗药物的现状。为每个免疫靶点提供了临床前的基本原理,包括主要表达和功能。讨论了临床意义和初步可用的试验结果,最后我们反思了该领域未来的期望和挑战。

专家意见

已经在三阴性乳腺癌中研究了几种免疫策略,包括 PD1-PD-L1 轴以外的共抑制分子、共刺激检查点、癌症疫苗、过继细胞转移、联合疗法以及不同的给药途径。大多数方法在早期临床试验中显示出抗癌活性和良好的安全性。由于免疫检查点抑制剂迄今为止仅对一小部分三阴性乳腺癌患者有效,因此确定预测性生物标志物是优先事项,以完善患者选择。来自正在进行的临床试验的数据,以及对乳腺肿瘤免疫微环境的逐渐改善的解释,有望完善新的免疫靶点在治疗三阴性乳腺癌中的作用。

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