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CAR-T 细胞治疗肺癌:潜力与前景

英文原题:CAR-T cell therapy for lung cancer: Potential and perspective.

查看英文原题

CAR-T cell therapy for lung cancer: Potential and perspective.

PubMed 2022/03/15(内容时间) Thorac Cancer Q2 · IF 2.6(JCR 2025)

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中文摘要

肺癌是全球范围内发病率和死亡率最高的癌症。在当前免疫治疗时代,包括单克隆抗体靶向药物在内的越来越多免疫治疗药物已用于恶性肿瘤的临床治疗,但仍存在许多局限性。嵌合抗原受体修饰T(CAR-T)细胞作为一种新型过继性免疫治疗策略,不仅已成功用于血液系统肿瘤,也为包括肺癌在内的实体瘤免疫治疗开辟了新途径。

然而,利用工程化CAR-T 细胞靶向肺癌特异性抗原面临诸多复杂问题,包括缺乏合适的肿瘤特异性抗原、免疫抑制性肿瘤微环境、CAR-T 细胞向肿瘤组织浸润水平低以及脱靶效应等。

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限。在本综述中,我们概述了CAR-T 细胞的基本结构和代际特征,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,并指出了当前面临的挑战和新的策略,旨在为CAR-T 细胞治疗肺癌的临床前实验和临床试验提供新的思路和方法。

展开英文摘要原文

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.

论文信息

作者
Chen L、Chen F、Li J、Pu Y、Yang C、Wang Y、Lei Y、Huang Y
第一作者单位
Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China.China
通讯作者单位
Department of Thoracic Surgery I, Key Laboratory of Lung Cancer of Yunnan Province, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China.China
文献类型
综述 · 非美国政府资助研究
期刊
Thoracic cancer2022 Apr
原文标识
PubMed 35289077 · DOI 10.1111/1759-7714.14375