Mansoori Shafieeh, Noei Ahmad, Maali Amirhosein, Seyed-Motahari Seyedeh Sheila, Sharifzadeh Zahra
Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
Department of Medical Biotechnology, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Cancer Cell Int. 2024 Sep 3;24(1):304. doi: 10.1186/s12935-024-03479-y.
CAR-T cell therapy is known as an effective therapy in patients with hematological malignancies. Since 2017, several autologous CAR-T cell (auto-CAR-T) drugs have been approved by the US Food and Drug Administration (FDA) for the treatment of some kinds of relapsed/refractory hematological malignancies. However, some patients fail to respond to these drugs due to high manufacturing time, batch-to-batch variation, poor quality and insufficient quantity of primary T cells, and their insufficient expansion and function. CAR-T cells prepared from allogeneic sources (allo-CAR-Ts) can be an alternative option to overcome these obstacles. Recently, several allo-CAR-Ts have entered into the early clinical trials. Despite their promising preclinical and clinical results, there are two main barriers, including graft-versus-host disease (GvHD) and allo-rejection that may decline the safety and efficacy of allo-CAR-Ts in the clinic. The successful development of these products depends on the starter cell source, the gene editing method, and the ability to escape immune rejection and prevent GvHD. Here, we summarize the gene editing technologies and the potential of various cell sources for developing allo-CAR-Ts and highlight their advantages for the treatment of hematological malignancies. We also describe preclinical and clinical data focusing on allo-CAR-T therapy in blood malignancies and discuss challenges and future perspectives of allo-CAR-Ts for therapeutic applications.
嵌合抗原受体T细胞（CAR-T）疗法是治疗血液系统恶性肿瘤患者的一种有效疗法。自2017年以来，几种自体CAR-T细胞（auto-CAR-T）药物已获美国食品药品监督管理局（FDA）批准，用于治疗某些复发/难治性血液系统恶性肿瘤。然而，由于制备时间长、批次间差异大、原代T细胞质量差且数量不足，以及其扩增和功能不足，一些患者对这些药物没有反应。从异基因来源制备的CAR-T细胞（allo-CAR-T）可能是克服这些障碍的一种替代选择。最近，几种allo-CAR-T已进入早期临床试验。尽管它们在临床前和临床研究中取得了有前景的结果，但仍存在两个主要障碍，包括移植物抗宿主病（GvHD）和异基因排斥，这可能会降低allo-CAR-T在临床上的安全性和有效性。这些产品的成功开发取决于起始细胞来源、基因编辑方法以及逃避免疫排斥和预防GvHD的能力。在此，我们总结了用于开发allo-CAR-T的基因编辑技术和各种细胞来源的潜力，并强调它们在治疗血液系统恶性肿瘤方面的优势。我们还描述了聚焦于血液恶性肿瘤中allo-CAR-T疗法的临床前和临床数据，并讨论了allo-CAR-T在治疗应用中的挑战和未来前景。
