肿瘤细胞治疗研究
英文原题：Chimeric antigen receptor T cells targeting FcRH5 provide robust tumour-specific responses in murine xenograft models of multiple myeloma.
这些发现表明，以FcRH5为靶点的CAR-T细胞可能代表MM的一种有前景的治疗途径。
靶向BCMA的嵌合抗原受体（CAR）T细胞疗法在多发性骨髓瘤（MM）中展现出显著的临床反应。然而，部分BCMA缺陷型肿瘤患者无法从该疗法中获益，另一些患者则可能因BCMA抗原丢失而导致复发，因此有必要鉴定额外的CAR-T靶点。在此，我们证明FcRH5在多发性骨髓瘤细胞上表达，并可作为CAR-T细胞的靶点。FcRH5 CAR-T细胞对MM细胞表现出抗原特异性激活、细胞因子分泌和细胞毒性。此外，FcRH5 CAR-T细胞在小鼠异种移植模型中展现出强效的杀肿瘤活性，包括在BCMA表达缺陷的模型中。我们还证明，不同形式的可溶性FcRH5可干扰FcRH5 CAR-T细胞的疗效。最后，FcRH5/BCMA双特异性CAR-T细胞能有效识别表达FcRH5和/或BCMA的MM细胞，并在体内展现出优于单特异性CAR-T细胞的疗效。这些发现表明，利用CAR-T细胞靶向FcRH5可能代表一种有前景的MM治疗途径。
BCMA-targeting chimeric antigen receptor (CAR) T cell therapy demonstrates impressive clinical response in multiple myeloma (MM). However, some patients with BCMA-deficient tumours cannot benefit from this therapy, and others can experience BCMA antigen loss leading to relapse, thus necessitating the identification of additional CAR-T targets. Here, we show that FcRH5 is expressed on multiple myeloma cells and can be targeted with CAR-T cells. FcRH5 CAR-T cells elicited antigen-specific activation, cytokine secretion and cytotoxicity against MM cells. Moreover, FcRH5 CAR-T cells exhibited robust tumoricidal efficacy in murine xenograft models, including one deficient in BCMA expression. We also show that different forms of soluble FcRH5 can interfere with the efficacy of FcRH5 CAR-T cells. Lastly, FcRH5/BCMA-bispecific CAR-T cells efficiently recognized MM cells expressing FcRH5 and/or BCMA and displayed improved efficacy, compared with mono-specific CAR-T cells in vivo. These findings suggest that targeting FcRH5 with CAR-T cells may represent a promising therapeutic avenue for MM.
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