Zabaleta Aintzane, Blanco Laura, Kim Peter S, Bisht Kamlesh, Wang Hongfang, Van de Velde Helgi, Lasa Marta, Tamariz-Amador Luis-Esteban, Rodriguez-Otero Paula, San-Miguel Jesús, Paiva Bruno, Martín-Sánchez Esperanza
Cancer Center Clinica Universidad de Navarra (CCUN), Centro de Investigacion Medica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IdiSNA), CIBER-ONC Numbers CB16/12/00369 and CB16/12/00489, Pamplona, Spain.
Sanofi R&D, Cambridge, Massachusetts, USA.
Br J Haematol. 2024 Dec;205(6):2262-2267. doi: 10.1111/bjh.19784. Epub 2024 Sep 22.
There is accumulating evidence of BCMA and GPRC5D loss after treatment with T-cell redirecting therapies in patients with relapsed/refractory multiple myeloma (RRMM). While complete CD38 loss is not observed upon relapses after treatment with anti-CD38 monoclonal antibodies (mAb), there is downregulation of surface CD38 expression and decreased number and function of NK cells, which renders these patients resistant to retreatment with anti-CD38 mAb. Here, we provide preclinical evidence that RRMM patients previously exposed to anti-CD38 mAb could benefit from T-cell-based immunotherapy that depend less on CD38 antigen density and NK-cell activity, such as the novel CD38/CD3xCD28 trispecific T-cell engager, SAR442257.
越来越多的证据表明，复发/难治性多发性骨髓瘤（RRMM）患者接受T细胞重定向疗法治疗后会出现BCMA和GPRC5D缺失。虽然抗CD38单克隆抗体（mAb）治疗后复发时未观察到CD38完全缺失，但表面CD38表达下调，NK细胞数量和功能降低，这使得这些患者对再次使用抗CD38 mAb治疗产生耐药性。在此，我们提供临床前证据表明，先前接受过抗CD38 mAb治疗的RRMM患者可能受益于较少依赖CD38抗原密度和NK细胞活性的基于T细胞的免疫疗法，例如新型CD38/CD3xCD28三特异性T细胞衔接器SAR442257。
