Serum B-cell maturation antigen (BCMA) reduces binding of anti-BCMA antibody to multiple myeloma cells
Serum B-cell maturation antigen (BCMA) reduces binding of anti-BCMA antibody to multiple myeloma cells
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DOI：
10.1016/j.leukres.2019.04.008
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发表时间：
2019-06-01
影响因子：
2.7
通讯作者：
Berenson, James R.
中科院分区：
文献类型：
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作者：
Chen, Haiming;Li, Mingjie;Berenson, James R.
B细胞成熟抗原（BCMA）是肿瘤坏死因子受体（TNFR）家族成员，选择性表达于终末分化的B淋巴细胞，包括多发性骨髓瘤（MM）肿瘤细胞。我们试图确定MM血清中的循环（c）BCMA是否干扰抗BCMA抗体与MM细胞的结合。采用酶联免疫吸附试验（ELISA）测定379例复发/难治性MM（RRMM）患者的血清BCMA水平。此外，使用流式细胞术和免疫荧光研究来检查患者血清中的BCMA浓度是否足够高以干扰抗BCMA抗体与MM肿瘤细胞的结合。我们已经表明MM患者血清中BCMA升高，RRMM患者sBCMA的中位浓度为176 ng/mL（n=379）。此外，抗BCMA抗体与MM肿瘤细胞的结合一致降低，sBCMA水平>= 156 ng/mL。总之，这些结果表明，大多数RRMM患者的循环BCMA水平足够高，足以干扰抗BCMA抗体与MM肿瘤细胞的结合，并可能干扰BCMA靶向免疫治疗。
B-cell maturation antigen (BCMA), a tumor necrosis factor receptor (TNFR) family member, is selectively expressed on terminally differentiated B-lymphocytes including multiple myeloma (MM) tumor cells. We sought to determine whether circulating (c) BCMA in MM serum interferes with antiBCMA antibody binding to MM cells. An enzyme-linked immunosorbent assay (ELISA) was used to determine serum (s) BCMA levels among 379 samples from patients with relapsed/refractory MM (RRMM). Furthermore, flow cytometric and immunofluorescent studies were used to examine if concentrations of BCMA in patients' serum were high enough to interfere with the binding of anti-BCMA antibody to MM tumor cells. We have shown that BCMA is elevated in the serum from MM patients and that the median concentration of sBCMA from RRMM patients was 176 ng/mL (n=379). Additionally, there was a consistent decrease in the binding of anti-BCMA antibody to MM tumor cells with sBCMA level >= 156 ng/mL. Together, these results demonstrate that circulating BCMA levels in most RRMM patients are high enough to interfere with anti-BCMA antibody binding to MM tumor cells and may interfere with BCMA-targeted immune-based therapies.