Du Zhicheng, Zhu Sumin, Zhang Xi, Gong Zhiyuan, Wang Shu
Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
Cancers (Basel). 2023 Jan 17;15(3):567. doi: 10.3390/cancers15030567.
MM, characterized by the progressive accumulation of clonal plasma cells in bone marrow, remains a severe medical problem globally. Currently, almost all MM patients who have received standard treatments will eventually relapse. Autologous anti-BCMA CAR-T cells are one of the FDA-approved immunotherapy cell-based products for treating adults with relapsed or refractory (r/r) multiple myeloma. However, this type of CAR-T cell product has several limitations, including high costs, long manufacturing times, and possible manufacturing failure, which significantly hinder its wider application for more patients. In this review, we summarized the current development stage of applying other types of immune cells to bring the anti-BCMA CAR-T therapy from autologous to allogeneic. In general, anti-BCMA CAR gene-edited αβ T cells and CAR-Natural Killer (NK) cells are at the forefront, with multiple clinical trials ongoing, while CAR-γδ T cells and CAR-invariant Natural Killer T (iNKT) cells are still in pre-clinical studies. Other immune cells such as macrophages, B cells, and dendritic cells have been mainly developed to target other antigens and have the potential to be used to target BCMA. Nevertheless, additional regulatory requirements might need to be taken into account in developing these non-conventional allogenic anti-BCMA CAR-based cell products.
多发性骨髓瘤(MM)的特征是骨髓中克隆性浆细胞进行性积聚,在全球范围内仍然是一个严重的医学问题。目前,几乎所有接受标准治疗的MM患者最终都会复发。自体抗BCMA嵌合抗原受体T细胞(CAR-T)是美国食品药品监督管理局(FDA)批准的用于治疗复发或难治性(r/r)成年多发性骨髓瘤的基于免疫疗法的细胞产品之一。然而,这类CAR-T细胞产品存在一些局限性,包括成本高、生产时间长以及可能出现生产失败等问题,这严重阻碍了其在更多患者中的广泛应用。在这篇综述中,我们总结了应用其他类型免疫细胞将抗BCMA CAR-T疗法从自体转变为异体的当前发展阶段。总体而言,抗BCMA CAR基因编辑的αβ T细胞和CAR-自然杀伤(NK)细胞处于前沿,多项临床试验正在进行中,而CAR-γδ T细胞和CAR-不变自然杀伤T(iNKT)细胞仍处于临床前研究阶段。其他免疫细胞,如巨噬细胞、B细胞和树突状细胞,主要是针对其他抗原进行开发,并且有可能用于靶向BCMA。尽管如此,在开发这些基于非传统异体抗BCMA CAR的细胞产品时,可能需要考虑额外的监管要求。
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