[摘 要] 血液系统恶性肿瘤严重威胁人类健康，CAR-T细胞疗法是治疗血液系统恶性肿瘤的有效方法，是近年来发展最为迅 猛的肿瘤免疫治疗方法之一。为获得高效低毒的CAR-T细胞，经过不断发展及探索，CAR-T细胞疗法在血液恶性肿瘤中取得了 一系列重大突破，包括人源化CAR-T细胞技术、双靶点及多靶点CAR-T细胞技术、通用型CAR-T细胞技术和CAR-T细胞联合策 略技术。人源化CAR-T细胞技术通过人源化改造，降低其免疫原性；双靶点及多靶点CAR-T细胞技术能够同时识别两种或多种 肿瘤相关抗原，减少抗原逃逸，提高疗效；通用型CAR-T细胞技术解决了成本高及可及性等问题；CAR-T细胞联合策略技术通过 不同治疗方式的组合 ，有效解决了一部分 CAR-T 细胞后复发等问题，提高了其疗效和安全性等。尽管CAR-T细胞疗法在 血液恶性肿瘤治疗中取得了重大突破，但仍然面临着耐药与抗原逃逸、细胞毒性和治疗后复发等问题。本文介绍CAR-T细胞精 准治疗血液恶性肿瘤进程中的重大突破成果及存在的问题与解决对策。

[Abstract] Hematologic malignancies are a severe threat to human health. CAR-T cell therapy, as a highly effective treatment for hematologic malignancies, has become one of the fastest developing cancer immunotherapies in recent years. To obtain highly effective and low-toxicity CAR-T cells, through continuous development and exploration, CAR-T cell therapy has achieved a series of significant breakthroughs in treating hematologic malignancies, including humanized CAR-T cell technology, dual-target and multitarget CAR-T cell technology, universal CAR-T cell technology, and CAR-T cell combination strategy technology. Humanized CAR-T cell technology reduces immunogenicity through humanized modification. Dual-target and multi-target CAR-T cell technology recognizes two or more tumor antigens, minimizes antigen escape and enhance efficacy. Universal CAR-T cell technology solves problems such as high cost and accessibility issues. The CAR-T cell combination strategy technology effectively deals with CAR-T recurrence and enhances efficacy and safety by combining different treatment methods. Although CAR-T cell therapy has achieved significant breakthroughs in the treatment of hematologic malignancies, it still faces challenges such as drug resistance, antigen escape, cytotoxicity, and posttreatment recurrence. This review presents the significant breakthroughs, existing problems, and solutions for CAR-T cell precise therapy for hematological malignancies.

国家自然科学基金（No.82270233）