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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:T-cell engagers in cancer immunotherapy: mechanisms, challenges, and future perspectives.
T-cell engagers in cancer immunotherapy: mechanisms, challenges, and future perspectives.
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T细胞衔接器(TCE)是一类快速发展的癌症免疫疗法,可不依赖MHC抗原呈递,将细胞毒性T细胞重定向至肿瘤相关抗原。本综述概述多种TCE平台的开发、结构形式及治疗潜力,包括双特异性(BiTE)和三特异性T细胞衔接器(TriTE)、双亲和力重定向分子(DART)及其他新兴形式。我们还介绍了以blinatumomab和teclistamab等药物为代表的血液系统恶性肿瘤治疗临床成功。与此同时,本文讨论实体瘤中的持续挑战,如抗原异质性和免疫抑制性肿瘤微环境,并从疗效、安全性、毒性、耐药及成本等方面与CAR-T 细胞疗法进行比较。提高特异性和降低毒性的策略包括肿瘤选择性活化(如XPAT)、调节CD3亲和力及多功能构建体。未来方向包括人工智能驱动设计、合成生物学及肿瘤学以外的潜在应用,如自身免疫病和感染性疾病。作为可规模化生产的现货型疗法,T细胞衔接器有望成为个体化、可及癌症治疗的重要工具。
T-cell engagers (TCEs) are a rapidly evolving class of cancer immunotherapies that redirect cytotoxic T cells to tumor-associated antigens independently of MHC presentation. This review outlines the development, structural formats, and therapeutic potential of various TCE platforms, including bispecific (BiTEs) and trispecific T-cell engagers (TriTEs), dual affinity re-targeting (DART), and other emerging formats.
We also highlight the clinical success in treating hematologic malignancies as demonstrated by agents such as blinatumomab and teclistamab.
We also discussed the ongoing challenges in solid tumors, such as antigen heterogeneity and the immunosuppressive tumor microenvironment. A comparative analysis with CAR-T cell therapies is provided, with a focus on efficacy, safety, toxicity, resistance, and cost. Strategies to increase specificity and reduce toxicity, such as tumor-selective activation (e. g.
, XPATs), CD3 affinity tuning, and multifunctional constructs, are discussed. Future directions include AI-driven design, synthetic biology, and potential applications beyond oncology, including autoimmune and infectious diseases. As scalable, off-the-shelf therapeutics, T-cell engagers are poised to become essential tools in personalized and accessible cancer treatment.
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