Marta Śledź, Alicja Wojciechowska, Radosław Zagożdżon, Beata Kaleta
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引用次数: 0
摘要
嵌合抗原受体- t (CAR-T)细胞疗法已成为治疗许多血液系统恶性肿瘤的成功选择,但也为一系列非恶性疾病带来了希望。然而,在传统的方法中,CAR-T细胞的产生与患者淋巴细胞的分离、体外修饰、扩增和输注回患者血液有关。这种经典协议复杂、耗时且昂贵。这些问题可以通过使用病毒平台或非病毒传递系统原位生产CAR- t细胞、CAR-自然杀伤细胞或CAR-巨噬细胞的成功方案来解决。此外,研究表明,原位CAR-T诱导可能与CAR-T治疗相关的最常见毒性的风险降低有关,如细胞因子释放综合征、免疫效应细胞相关神经毒性综合征和“靶外肿瘤”毒性。本文综述了CAR-T细胞的现状和未来发展趋势。事实上,该领域的临床前工作,包括动物研究,为原位生成car -载体免疫效应细胞的前瞻性转化开发和实际医学验证策略带来了希望。
In Situ Programming of CAR-T Cells: A Pressing Need in Modern Immunotherapy
Chimeric antigen receptor-T (CAR-T) cell-based therapy has become a successful option for treatment of numerous hematological malignancies, but also raises hope in a range of non-malignant diseases. However, in a traditional approach, generation of CAR-T cells is associated with the separation of patient’s lymphocytes, their in vitro modification, and expansion and infusion back into patient’s bloodstream. This classical protocol is complex, time-consuming, and expensive. Those problems could be solved by successful protocols to produce CAR-T cells, but also CAR-natural killer cells or CAR macrophages, in situ, using viral platforms or non-viral delivery systems. Moreover, it was demonstrated that in situ CAR-T induction may be associated with reduced risk of the most common toxicities associated with CAR-T therapy, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and “on-target, off-tumor” toxicity. This review aims to summarize the current state-of-the-art and future perspectives for the in situ-produced CAR-T cells. Indeed, preclinical work in this area, including animal studies, raises hope for prospective translational development and validation in practical medicine of strategies for in situ generation of CAR-bearing immune effector cells.
期刊介绍:
Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.