Teclistamab是一个活跃的T cell-redirecting双特异性抗体对成熟b细胞抗原多发性骨髓瘤。

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Pillarisetti K,权力G, Luistro L, Babich,鲍德温E,李Y,张X, Mendonca M,北京N, Nanjunda R,下巴D,小贩K,曾Y,玫瑰油R, Gaudet F

Teclistamab是一个活跃的T cell-redirecting双特异性抗体对成熟b细胞抗原多发性骨髓瘤。

血液放置于2020年9月22日;4 (18):4538 - 4549。doi: 10.1182 / bloodadvances.2020002393。

PubMed ID

32956453 (在PubMed

]

文摘

成熟B细胞抗原(BCMA)、肿瘤坏死因子受体家族成员,主要表达在终末分化B细胞的表面。BCMA高度表达plasmablasts和浆细胞从多发性骨髓瘤(MM)患者样本。我们开发了一个BCMAxCD3双特异性抗体(teclistamab [johnson & johnson - 64007957])招募并激活T细胞杀死BCMA-expressing MM细胞。Teclistamab诱导的细胞毒性BCMA + MM细胞株体外(H929细胞,50%有效浓度(EC50) = 0.15 nM;MM.1R细胞,EC50 = 0.06 nM;RPMI 8226个细胞,随之而来的EC50 = 0.45海里)t细胞激活(EC50 = 0.21 nM H929细胞;MM.1R细胞,EC50 = 0.1 nM;RPMI 8226个细胞,EC50 = 0.28海里)和细胞因子释放。这个活动是进一步提高γ分泌酶抑制剂的存在(ly - 411575)。Teclistamab也耗尽BCMA +细胞在骨髓样本MM患者在体外测定平均EC50值1.7海里。 Under more physiological conditions using healthy human whole blood, teclistamab mediated dose-dependent lysis of H929 cells and activation of T cells. Antitumor activity of teclistamab was also observed in 2 BCMA+ MM murine xenograft models inoculated with human T cells (tumor inhibition with H929 model and tumor regression with the RPMI 8226 model) compared with vehicle and antibody controls. The specific and potent activity of teclistamab against BCMA-expressing cells from MM cell lines, patient samples, and MM xenograft models warrant further evaluation of this bispecific antibody for the treatment of MM. Phase 1 clinical trials (monotherapy, #NCT03145181; combination therapy, #NCT04108195) are ongoing for patients with relapsed/refractory MM.

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药物

Teclistamab

药物靶点

药物	目标	类	生物	药理作用	行动
Teclistamab	t细胞表面糖蛋白CD3(蛋白质组)	蛋白质组	人类	是的	抗体	细节
Teclistamab	肿瘤坏死因子受体超家族成员17	蛋白质	人类	是的	抗体	细节