细胞毒性
抗原
流式细胞术
癌症研究
抗体
多发性骨髓瘤
克隆形成试验
等离子体电池
医学
免疫学
生物
细胞
体外
生物化学
作者
Lydia Lee,Danton Bounds,Jennifer C. Paterson,Gaëlle Herledan,Katherine Sully,Laura Seestaller‐Wehr,William Fieles,James Tunstead,Lee McCahon,Fiona Germaschewski,Patrick A. Mayes,Jenny Craigen,Manuel Rodríguez-Justo,Kwee Yong
摘要
Summary B‐cell maturation antigen ( BCMA , also termed TNFRSF 17) is an attractive therapeutic target due to its restricted expression on normal and malignant plasma cells ( PC ). GSK 2857916 (or J6M0‐ MMAF ) is a BCMA ‐specific antibody conjugated to the microtubule‐disrupting agent monomethyl auristatin F ( MMAF ) via a protease‐resistant linker. To evaluate the clinical potential of this agent, tumour cells from seventy multiple myeloma ( MM ) patients were assessed for BCMA expression by immunohistochemistry and flow cytometry. All patients tested expressed BCMA , at varying levels, and both surface and intracellular expression were observed. BCMA expression is maintained through relapse, extramedullary spread and in residual disease post therapy. BCMA levels may also be prognostically useful as higher levels of BCMA were associated with poorer outcomes, even taking into account genetic risk. We observed rapid internalization of surface BCMA and newly expressed protein by 1 h, suggesting a mechanism for J6M0‐ MMAF activity even with low surface antigen. J6M0‐ MMAF mediated cytotoxicity of MM cells varied with dose and antigen levels, with clonogenic progenitors killed at lower doses than mature cells. In comparison, J6M0‐ MMAF killing of primary CD 138 + myeloma cells occurred with slower kinetics. Our observations support BCMA to be a promising therapeutic target in MM for novel therapies such as J6M0‐ MMAF .
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