CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Advancements and challenges in CAR-T cell therapy for solid tumors: A comprehensive review of antigen targets, strategies, and future directions.
Advancements and challenges in CAR-T cell therapy for solid tumors: A comprehensive review of antigen targets, strategies, and future directions.
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最初用于治疗血液系统恶性肿瘤的 CAR-T 近年来在实体瘤治疗方面取得显著进展。目前,第二代 CAR-T 已进入临床应用,第五代 CAR-T 正在积极开发。但实体瘤早期临床试验成功有限,主要原因是肿瘤免疫抑制性微环境以及肿瘤特异性抗原稀少。尽管如此,联合疗法和基因编辑等新兴策略显示出增强 CAR-T 效力的潜力。本综述全面考察 CAR-T 治疗实体瘤的研究现状,重点关注实体瘤中已探索的各类抗原靶点。作者批判性回顾已建立和新型靶点,阐述其治疗潜力和局限,并指出目前阻碍实体瘤 CAR-T 成功的关键挑战,包括靶抗原选择、物理屏障、抗原逃逸、免疫抑制性微环境及不良反应。尽管 CAR-T 治疗实体瘤仍面临严峻挑战,持续研究正推动其融入主流癌症治疗体系,为改善实体恶性肿瘤患者结局带来新希望。
Chimeric antigen receptor-modified T cell therapy, originally employed in hematological malignancies treatment, has made significant strides in addressing solid tumors in recent years. Presently, second-generation CAR-T therapy has reached clinical implementation, while fifth-generation CAR-T therapy is in active development.
However, initial clinical trials in solid tumors have shown limited success, primarily due to the immunosuppressive microenvironment of the tumor and the scarcity of tumor-specific antigens. Nevertheless, emerging strategies, including combination therapies and gene editing technologies, exhibit promising potential in enhancing CAR-T cell effectiveness.
In this review, we comprehensively examine the current state of research on CAR-T cell therapy for solid tumors, with a particular focus on the various antigenic targets that have been explored for solid tumors.
We critically review established and novel targets, providing insights into their therapeutic potential and limitations.
Additionally, we highlight the key challenges that currently hinder the success of CAR-T therapy in solid tumors, including the choice of target antigens, physical barriers, antigen escape, immunosuppressive microenvironment, and adverse reactions. Despite the formidable challenges confronting CAR-T cell therapy in solid tumors, ongoing research is forging a path towards its integration into the mainstream cancer treatment paradigm, offering renewed optimism for enhanced outcomes in patients afflicted with solid malignancies.
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