肿瘤细胞治疗研究
英文原题：Limited expression of B-cell maturation antigen in acute myeloid leukemia.
我们的数据表明，BCMA 在 AML 中的表达是受限的，而 BCMA-19F2 不适用于 AML 样本背景下的 BCMA 检测。
B细胞成熟抗原（BCMA）最近被确定为急性髓系白血病（AML）T细胞导向治疗的靶点，其依据是一项研究，该研究使用流式细胞术抗BCMA抗体克隆19F2（BCMA-19F2）报告AML细胞中BCMA丰度高。然而，我们通过分析已建立的转录组谱进行的独立研究表明，AML患者样本和AML细胞系中BCMA水平均有限。AML细胞中BCMA低表达通过使用替代抗BCMA抗体（克隆REA315）的流式细胞术和western blotting得到验证。重要的是，我们揭示BCMA-19F2可通过其非抗原结合片段非特异性结合AML细胞，同型对照实验和Fc受体阻断实验证实了这一点。此外，细胞毒性实验证实，抗BCMA CAR T细胞治疗对白血病细胞裂解作用极小。我们的数据表明，BCMA表达在AML中受限，BCMA-19F2不适合在AML样本背景下检测BCMA。这强调，准确评估肿瘤抗原对于治疗靶点设计至关重要。
B-cell maturation antigen (BCMA) was recently identified as a target of T-cell-directed therapy for acute myeloid leukemia (AML), based on the study reporting high BCMA abundance in AML cells using the flow cytometry anti-BCMA antibody clone 19F2 (BCMA-19F2). However, our independent investigation demonstrated limited BCMA levels in both AML patient samples and AML cell lines through the analysis of established transcriptome profiles. The low BCMA expression in AML cells was validated by flow cytometry using an alternative anti-BCMA antibody (clone REA315) and western blotting. Importantly, we unveiled that the BCMA-19F2 could bind non-specifically to AML cells via its non-antigen-binding fragment, as evidenced by the isotype control experiment and Fc receptor blocking assay. Furthermore, cytotoxicity assay confirmed that the leukemic cell lysis was minimal on the treatment of anti-BCMA CAR T cells. Our data suggest that BCMA expression is restricted in AML, and the BCMA-19F2 is unsuitable for BCMA detection in the context of AML samples. It underscores that the accurate assessment of tumor antigen is paramount for therapeutic target design.
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