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释放 CAR-T 细胞治疗的潜力:血液肿瘤与实体瘤治疗中的进展、挑战与未来方向

英文原题:Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments.

PubMed 2023/07/07(内容时间) J Transl Med Q1 · IF 9.7(JCR 2025)

研究概要

传统癌症治疗使用非特异性药物和单克隆抗体靶向肿瘤细胞。

中文摘要

传统癌症治疗使用非特异性药物和单克隆抗体靶向肿瘤细胞。然而,嵌合抗原受体(CAR)-T细胞疗法利用免疫系统的T细胞来识别和攻击肿瘤细胞。T细胞从患者体内分离出来,经过改造以靶向肿瘤相关抗原。CAR-T疗法通过靶向CD-19和B细胞成熟抗原,已获得FDA批准用于治疗血液系统恶性肿瘤,如B细胞急性淋巴细胞白血病、大B细胞淋巴瘤和多发性骨髓瘤。双特异性嵌合抗原受体可能有助于减轻肿瘤抗原逃逸,但在某些肿瘤细胞不表达靶抗原的情况下,其疗效可能有限。尽管在血液系统恶性肿瘤中取得了成功,CAR-T技术在实体瘤中仍面临挑战,包括缺乏可靠的肿瘤相关抗原、缺氧核心、免疫抑制性肿瘤环境、活性氧增强以及T细胞浸润减少。为克服这些挑战,当前研究旨在识别可靠的肿瘤相关抗原,并开发具有成本效益、肿瘤微环境特异性的CAR-T细胞。本综述涵盖了CAR-T疗法针对各种肿瘤的演变,包括血液系统恶性肿瘤和实体瘤,重点阐述了CAR-T细胞疗法面临的挑战,并提出了克服这些障碍的策略,例如利用单细胞RNA测序和人工智能来优化临床级CAR-T细胞。

展开英文摘要原文

Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)-T cell therapy, however, leverages the immune system's T-cells to recognize and attack tumor cells. T-cells are isolated from patients and modified to target tumor-associated antigens. CAR-T therapy has achieved FDA approval for treating blood cancers like B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma by targeting CD-19 and B-cell maturation antigens. Bi-specific chimeric antigen receptors may contribute to mitigating tumor antigen escape, but their efficacy could be limited in cases where certain tumor cells do not express the targeted antigens. Despite success in blood cancers, CAR-T technology faces challenges in solid tumors, including lack of reliable tumor-associated antigens, hypoxic cores, immunosuppressive tumor environments, enhanced reactive oxygen species, and decreased T-cell infiltration. To overcome these challenges, current research aims to identify reliable tumor-associated antigens and develop cost-effective, tumor microenvironment-specific CAR-T cells. This review covers the evolution of CAR-T therapy against various tumors, including hematological and solid tumors, highlights challenges faced by CAR-T cell therapy, and suggests strategies to overcome these obstacles, such as utilizing single-cell RNA sequencing and artificial intelligence to optimize clinical-grade CAR-T cells.

论文信息

作者
Dagar G、Gupta A、Masoodi T、Nisar S、Merhi M、Hashem S、Chauhan R、Dagar M
第一作者单位
Department of Medical Oncology (Lab.), Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, Delhi, 110029, India.India
通讯作者单位
Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, P.O. Box 26999, Doha, Qatar. abhat@sidra.org.
文献类型
综述 · 非美国政府资助研究
期刊
Journal of translational medicine2023 Jul 7
原文标识
PubMed 37420216 · DOI 10.1186/s12967-023-04292-3