Srivastava Shivani, Tyagi Anuradha, Pawar Vishakha Anand, Khan Nawaid Hussain, Arora Kavita, Verma Chaitenya, Kumar Vinay
Department of Pathology, School of Medicine, Yale University, New Haven, CT, USA.
Department of cBRN, Institute of Nuclear Medicine and Allied Science, Delhi, India.
Immunotargets Ther. 2024 Aug 27;13:413-433. doi: 10.2147/ITT.S474659. eCollection 2024.
The CAR-T cell therapy has marked the dawn of new era in the cancer therapeutics and cell engineering techniques. The review emphasizes on the challenges that obstruct the therapeutic efficiency caused by cell toxicities, immunosuppressive tumor environment, and decreased T cell infiltration. In the interest of achieving the overall survival (OS) and event-free survival (EFS) of patients, the conceptual background of potential target selection and various CAR-T cell design techniques are described which can minimize the off-target effects, reduce toxicity, and thus increase the resilience of CAR-T cell treatment in the haematological malignancies as well as in solid tumors. Furthermore, it delves into cutting-edge technologies like gene editing and synthetic biology, providing new opportunities to enhance the functionality of CAR-T cells and overcome mechanisms of immune evasion. This review provides a comprehensive understanding of the complex and diverse aspects of CAR-T cell-based gene treatments, including both scientific and clinical aspects. By effectively addressing the obstacles and utilizing the capabilities of cutting-edge technology, CAR-T cell therapy shows potential in fundamentally changing immunotherapy and reshaping the approach to cancer treatment.
嵌合抗原受体T细胞（CAR-T）疗法标志着癌症治疗和细胞工程技术新时代的曙光。这篇综述着重阐述了由细胞毒性、免疫抑制性肿瘤微环境以及T细胞浸润减少所导致的阻碍治疗效果的挑战。为了实现患者的总生存期（OS）和无事件生存期（EFS），本文描述了潜在靶点选择的概念背景以及各种CAR-T细胞设计技术，这些技术可以将脱靶效应降至最低，降低毒性，从而提高CAR-T细胞治疗在血液系统恶性肿瘤以及实体瘤中的适应性。此外，本文还深入探讨了基因编辑和合成生物学等前沿技术，这些技术为增强CAR-T细胞的功能和克服免疫逃逸机制提供了新机遇。这篇综述全面介绍了基于CAR-T细胞的基因治疗的复杂多样的各个方面，包括科学和临床方面。通过有效克服障碍并利用前沿技术的能力，CAR-T细胞疗法在从根本上改变免疫疗法和重塑癌症治疗方法方面显示出潜力。
