Zeltsman Masha, Dozier Jordan, McGee Erin, Ngai Daniel, Adusumilli Prasad S
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY.
Transl Res. 2017 Sep;187:1-10. doi: 10.1016/j.trsl.2017.04.004. Epub 2017 Apr 26.
Immunotherapy is a promising field that harnesses the power of the immune system as a therapeutic agent for cancer treatment. Beneficial outcomes shown in patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) with relatively higher tumor-infiltrating T cells, combined with impressive responses obtained in a cohort of patients with NSCLC following checkpoint blockade therapy, lays a strong foundation to promote effector immune responses in these patients. One such approach being investigated is administration of tumor antigen-targeted T cells with transduction of a chimeric antigen receptor (CAR). CARs are synthetic receptors that enhance T-cell antitumor effector function and have gained momentum to investigate in solid tumors based on recent successes of clinical trials treating patients with B-cell hematologic malignancies. This review summarizes target antigens for CAR T-cell therapy that are being investigated in preclinical studies and clinical trials for both NSCLC and MPM patients. We discuss the rationale for combination immunotherapies for NSCLC and MPM patients. Additionally, we have highlighted the challenges and strategies for overcoming the obstacles facing translation of CAR T-cell therapy to solid tumors.
免疫疗法是一个很有前景的领域,它利用免疫系统的力量作为癌症治疗的一种治疗手段。在肿瘤浸润性T细胞相对较多的非小细胞肺癌(NSCLC)和恶性胸膜间皮瘤(MPM)患者中显示出有益的结果,再加上在一组接受检查点阻断治疗的NSCLC患者中获得的令人印象深刻的反应,为促进这些患者的效应免疫反应奠定了坚实的基础。正在研究的一种方法是通过转导嵌合抗原受体(CAR)来给予肿瘤抗原靶向T细胞。CAR是增强T细胞抗肿瘤效应功能的合成受体,基于近期治疗B细胞血液系统恶性肿瘤患者的临床试验成功,在实体瘤研究方面获得了进展。这篇综述总结了正在NSCLC和MPM患者的临床前研究和临床试验中研究的CAR T细胞疗法的靶抗原。我们讨论了NSCLC和MPM患者联合免疫疗法的基本原理。此外,我们强调了将CAR T细胞疗法转化应用于实体瘤所面临的挑战和克服这些障碍的策略。