Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China.
Department of Nuclear Medicine, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China.
Thorac Cancer. 2022 Apr;13(7):889-899. doi: 10.1111/1759-7714.14375. Epub 2022 Mar 15.
Lung cancer is the highest incidence and mortality of all cancers around the world. In the present immunotherapy era, an increasing number of immunotherapeutic agents including monoclonal antibody-targeted drugs have been used in the clinical treatment of malignancy, but it still has many limitations. Chimeric antigen receptor-modified T (CAR-T) cells, a novel adoptive immunotherapy strategy, have not only been used successfully against hematological tumors, but have also opened up new avenues for immunotherapy of solid tumors, including lung cancer. However, targeting lung cancer-specific antigens using engineered CAR-T cells is complicated by the lack of proper tumor-specific antigens, an immunosuppressive tumor microenvironment, a low level of CAR-T cell infiltration into tumor tissues, along with off-target effect, etc. Simultaneously, the clinical application of CAR-T cells remains limited because of many challenges such as tumor lysis syndrome, neurotoxicity syndrome, and cytokine release syndrome. In this review, we outline the basic structure and generation characteristic of CAR-T cells and summarize the common tumor-associated antigens in clinical trials of CAR-T cell therapy for lung cancer, and point out the current challenges and new strategies, aiming to provide new ideas and approaches for the pre-clinical experiments and clinical trials of CAR-T cell therapy in lung cancer.
肺癌是全球所有癌症中发病率和死亡率最高的癌症。在当前的免疫治疗时代,越来越多的免疫治疗药物,包括单克隆抗体靶向药物,已被用于恶性肿瘤的临床治疗,但仍有许多局限性。嵌合抗原受体修饰的 T(CAR-T)细胞是一种新的过继免疫治疗策略,不仅成功地用于治疗血液肿瘤,而且为肺癌等实体肿瘤的免疫治疗开辟了新途径。然而,使用工程 CAR-T 细胞靶向肺癌特异性抗原存在诸多挑战,如缺乏适当的肿瘤特异性抗原、免疫抑制性肿瘤微环境、CAR-T 细胞在肿瘤组织中浸润程度低、脱靶效应等。同时,由于肿瘤溶解综合征、神经毒性综合征和细胞因子释放综合征等诸多挑战,CAR-T 细胞的临床应用仍然受到限制。本文概述了 CAR-T 细胞的基本结构和生成特性,并总结了 CAR-T 细胞治疗肺癌临床试验中常见的肿瘤相关抗原,指出了目前的挑战和新策略,旨在为肺癌 CAR-T 细胞治疗的临床前实验和临床试验提供新的思路和方法。