ABSTRACT

Introduction: Mesothelin (MSLN) is a tumor differentiation antigen normally restricted to the body’s mesothelial surfaces, but significantly overexpressed in a broad range of solid tumors. For this reason, MSLN has emerged as an important target for the development of novel immunotherapies. This review focuses on anti-MSLN chimeric antigen receptor (CAR) T cell immunotherapy approaches.

Areas covered: A brief overview of MSLN as a therapeutic target and existing anti-MSLN antibody-based drugs and vaccines is provided. A detailed account of anti-MSLN CAR-T cell approaches utilized in preclinical models is presented. Finally, a comprehensive summary of currently ongoing and completed anti-MSLN CAR-T cell clinical trials is discussed.

Expert opinion: Initial trials using anti-MSLN CAR-T cells have been safe, but efficacy has been limited. Employing regional routes of delivery, introducing novel modifications leading to enhanced tumor infiltration and persistence, and improved safety profiles and combining anti-MSLN CAR-T cells with standard therapies, could render them more efficacious in the treatment of solid malignancies.

摘要

简介：间皮素 (MSLN) 是一种肿瘤分化抗原，通常仅限于身体的间皮表面，但在广泛的实体瘤中显着过度表达。出于这个原因，MSLN 已成为开发新型免疫疗法的重要目标。本综述重点介绍抗 MSLN 嵌合抗原受体 (CAR) T 细胞免疫治疗方法。

涵盖的领域：简要概述了 MSLN 作为治疗靶点以及现有的基于抗 MSLN 抗体的药物和疫苗。详细介绍了在临床前模型中使用的抗 MSLN CAR-T 细胞方法。最后，讨论了当前正在进行和已完成的抗 MSLN CAR-T 细胞临床试验的综合总结。

专家意见：使用抗 MSLN CAR-T 细胞的初步试验是安全的，但疗效有限。采用区域递送途径、引入导致增强肿瘤浸润和持久性的新修饰、提高安全性以及将抗 MSLN CAR-T 细胞与标准疗法相结合，可以使它们在实体恶性肿瘤的治疗中更有效。