Thoracic malignancies (lung cancers and malignant pleural mesothelioma) are prevalent worldwide and are associated with high morbidity and mortality. Effective treatments are needed for patients with advanced disease. Cell therapies are a promising approach to the treatment of advanced cancers that make use of immune effector cells that have the ability to mediate antitumor immune responses. In this review, we discuss the prospect of chimeric antigen receptor-T (CAR-T) cells, natural killer (NK) cells, T cell receptor-engineered (TCR-T) cells, and tumor-infiltrating lymphocytes (TILs) as treatments for thoracic malignancies. CAR-T cells and TILs have proven successful in several hematologic cancers and advanced melanoma, respectively, but outside of melanoma, results have thus far been unsuccessful in most other solid tumors. NK cells and TCR-T cells are additional cell therapy platforms with their own unique advantages and challenges. Obstacles that must be overcome to develop effective cell therapy for these malignancies include selecting an appropriate target antigen, combating immunosuppressive cells and signaling molecules present in the tumor microenvironment, persistence, and delivering a sufficient quantity of antitumor immune cells to the tumor. Induced pluripotent stem cells (iPSCs) offer great promise as a source for both NK and T cell-based therapies due to their unlimited expansion potential. Here, we review clinical trial data, as well as recent basic scientific advances that offer insight into how we may overcome these obstacles, and provide an overview of ongoing trials testing novel strategies to overcome these obstacles.
胸部恶性肿瘤（肺癌和恶性胸膜间皮瘤）在全球范围内发病率高，且具有较高的发病率和死亡率。晚期疾病患者亟需有效治疗方案。细胞疗法作为一种利用具有介导抗肿瘤免疫应答能力的免疫效应细胞治疗晚期癌症的前沿手段，展现出巨大潜力。本综述探讨了嵌合抗原受体T细胞（CAR-T）、自然杀伤细胞（NK）、T细胞受体工程化T细胞（TCR-T）及肿瘤浸润淋巴细胞（TIL）在胸部恶性肿瘤治疗中的应用前景。CAR-T细胞和TIL已分别在多种血液系统恶性肿瘤和晚期黑色素瘤中取得显著成效，但在黑色素瘤以外的实体瘤治疗中尚未获得突破性进展。NK细胞与TCR-T细胞作为新兴的细胞治疗平台，各自具备独特优势并面临相应挑战。开发针对胸部恶性肿瘤的有效细胞疗法需克服多重障碍，包括选择合适靶向抗原、对抗肿瘤微环境中的免疫抑制细胞与信号分子、维持细胞持久性，以及确保足量抗肿瘤免疫细胞递送至肿瘤部位。诱导多能干细胞（iPSCs）因其无限扩增潜力，为NK细胞和T细胞疗法提供了极具前景的细胞来源。本文系统综述了相关临床试验数据及最新基础研究进展，深入探讨了克服这些障碍的潜在策略，并对当前正在开展的创新性临床试验进行了全面概述。
Engineered Cellular Therapies for the Treatment of Thoracic Cancers
肿瘤(癌症)患者之家