肿瘤细胞治疗研究
英文原题：A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers.
A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers.
我们报道了一种基于配体的 BAFF CAR-T，其能够结合三种不同受体，从而将 B 细胞肿瘤治疗中抗原逃逸的潜在可能降至最低。
B细胞活化因子（BAFF）可结合三种受体：BAFF-R、BCMA和TACI，这些受体主要表达于成熟B细胞。据报道，几乎所有B细胞肿瘤至少表达其中一种受体。本研究开发了一种基于BAFF配体的嵌合抗原受体（CAR），并采用非病毒基因递送方法制备BAFF CAR-T细胞。研究显示，BAFF CAR-T细胞可特异性结合上述三种BAFF受体，并能在体外及不同异种移植模型中有效杀伤多种B细胞肿瘤，包括套细胞淋巴瘤（MCL）、多发性骨髓瘤（MM）和急性淋巴细胞白血病（ALL）。BAFF CAR-T细胞与肿瘤细胞共培养后，CD69活化标志、CD107a脱颗粒标志及多种促炎细胞因子均增加。综上，本研究报道了一种基于配体的BAFF CAR-T，能够结合三种不同受体，有望降低B细胞肿瘤治疗中的抗原逃逸风险。
B cell-activating factor (BAFF) binds the three receptors BAFF-R, BCMA, and TACI, predominantly expressed on mature B cells. Almost all B cell cancers are reported to express at least one of these receptors. Here we develop a BAFF ligand-based chimeric antigen receptor (CAR) and generate BAFF CAR-T cells using a non-viral gene delivery method. We show that BAFF CAR-T cells bind specifically to each of the three BAFF receptors and are effective at killing multiple B cell cancers, including mantle cell lymphoma (MCL), multiple myeloma (MM), and acute lymphoblastic leukemia (ALL), in vitro and in vivo using different xenograft models. Co-culture of BAFF CAR-T cells with these tumor cells results in induction of activation marker CD69, degranulation marker CD107a, and multiple proinflammatory cytokines. In summary, we report a ligand-based BAFF CAR-T capable of binding three different receptors, minimizing the potential for antigen escape in the treatment of B cell cancers.
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