Bharadia Hetvi, Dabhade Akshada, Shah Aayushi C, Patel Rajanikant, Chorawala Mehul R, Patel Artiben, Shah Palak A
Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad, Gujarat, 380009, India.
Department of Product Development, Granules Pharmaceuticals Inc, 3701 Concorde Parkway, Chantilly, VA, 20151, USA.
Med Oncol. 2025 Aug 6;42(9):410. doi: 10.1007/s12032-025-02957-1.
Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a groundbreaking modality in cancer immunotherapy, offering remarkable clinical benefits, particularly in hematologic malignancies. By genetically reprogramming autologous T-cells to express synthetic receptors targeting tumor-specific antigens, CAR T-cells can mediate robust antitumor responses. This review provides a comprehensive overview of CAR T-cell immunotherapy, including its historical development, structural design, mechanism of action, and preclinical and clinical evolution. We highlight the intricacies of the tumor immune microenvironment, immune evasion mechanisms employed by cancer cells, and how CAR T-cells address these barriers. FDA-approved CAR T-cell therapies for B-cell malignancies and the current landscape of clinical trials for both liquid and solid tumors are critically analyzed. Furthermore, we explore novel targets, combination strategies, and technological innovations aimed at enhancing CAR T-cell efficacy and overcoming challenges related to antigen heterogeneity, toxicity, and resistance. Issues surrounding cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and tumor antigen escape are also discussed. The review delves into ongoing efforts in preclinical models, translational advancements, and emerging approaches such as dual-targeting CARs, armored CARs, and alternative co-stimulatory domains. Finally, the ethical, economic, and logistical challenges associated with CAR T-cell therapy are examined, including access disparities, manufacturing constraints, and the need for value-based pricing models. By synthesizing current insights and future directions, this review emphasizes transformative role of CAR T-cell therapy in oncology and the imperative for continued innovation to extend its benefits to broader patient populations.
嵌合抗原受体（CAR）T细胞疗法已成为癌症免疫治疗中的一种开创性模式，带来了显著的临床益处，尤其是在血液系统恶性肿瘤方面。通过对自体T细胞进行基因重编程，使其表达靶向肿瘤特异性抗原的合成受体，CAR T细胞可以介导强大的抗肿瘤反应。本综述全面概述了CAR T细胞免疫疗法，包括其历史发展、结构设计、作用机制以及临床前和临床进展。我们强调了肿瘤免疫微环境的复杂性、癌细胞采用的免疫逃逸机制，以及CAR T细胞如何应对这些障碍。对美国食品药品监督管理局（FDA）批准的用于B细胞恶性肿瘤的CAR T细胞疗法以及针对液体和实体瘤的当前临床试验情况进行了批判性分析。此外，我们探索了旨在提高CAR T细胞疗效并克服与抗原异质性、毒性和耐药性相关挑战的新靶点、联合策略和技术创新。还讨论了细胞因子释放综合征（CRS）、免疫效应细胞相关神经毒性综合征（ICANS）和肿瘤抗原逃逸等问题。本综述深入探讨了临床前模型中的持续努力、转化进展以及双靶点CAR、武装CAR和替代共刺激结构域等新兴方法。最后，研究了与CAR T细胞疗法相关的伦理、经济和后勤挑战，包括获取差异、生产限制以及基于价值的定价模型的必要性。通过综合当前的见解和未来方向，本综述强调了CAR T细胞疗法在肿瘤学中的变革性作用以及持续创新以将其益处扩展到更广泛患者群体的紧迫性。
