肿瘤细胞治疗研究
英文原题：Non-Conventional Allogeneic Anti-BCMA Chimeric Antigen Receptor-Based Immune Cell Therapies for Multiple Myeloma Treatment.
MM 以骨髓中克隆性浆细胞进行性蓄积为特征，在全球范围内仍是一个严峻的医学问题。
以骨髓中克隆性浆细胞进行性积累为特征的多发性骨髓瘤（MM），仍是全球严重的医疗问题。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 CAR-T细胞是FDA批准用于治疗成人复发或难治性（r/r）多发性骨髓瘤的一种基于细胞的免疫疗法产品。然而，这类CAR-T产品存在多项局限，包括成本高、制备时间长及可能制备失败，严重阻碍其进一步惠及更多患者。本综述总结利用其他类型免疫细胞，将抗BCMA CAR-T疗法从自体转为异体疗法的当前发展阶段。总体而言，抗BCMA基因编辑T细胞和CAR自然杀伤（NK）细胞处于研发前沿，并有多项临床试验进行中；CAR-γδ T细胞和CAR不变型自然杀伤T（iNKT）细胞仍处于临床前研究。其他免疫细胞，如巨噬细胞、B细胞和树突状细胞，主要被开发用于靶向其他抗原，也有望用于靶向BCMA。然而，开发这些非传统异体抗BCMA CAR细胞产品时，可能还需要考虑额外监管要求。
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 T cells and CAR-Natural Killer (NK) cells are at the forefront, with multiple clinical trials ongoing, while CAR- 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.
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