INTRODUCTIONCD38 and BCMA are proteins expressed at high levels in multiple myeloma cells, so they are targets for the development of mono- or multispecific antibodies.AREAS COVEREDPatent US20240132615 describes anti-CD3/BCMA/CD38 trispecific antibodies and a method of treating relapsed/refractory multiple myeloma pharmaceutically. In vitro and preclinical results show that anti-CD3/BCMA/CD38 trispecific antibodies have stronger binding affinity and killing potency compared to daratumumab, isatuximab, and teclistamab antibodies.EXPERT OPINIONThe trispecific structure and a silenced Fc are pharmaceutical advantages of the anti-CD3/BCMA/CD38 antibody for the treatment of relapsed or refractory multiple myeloma.

Cells

Pre-Clinical Assessment of SAR442257, a CD38/CD3xCD28 Trispecific T Cell Engager in Treatment of Relapsed/Refractory Multiple Myeloma

Article

作者: Van de Velde, Helgi ; Grab, Anna Luise ; John, Lukas ; Shome, Debarati ; Raab, Marc S. ; Gryzik, Stefanie ; Manta, Calin ; Wang, Hongfang ; Reijmers, Rogier M. ; Sarkar, Irene ; Kim, Peter S. ; Reichert, Philipp ; Bisht, Kamlesh ; Baumann, Anja ; Weinhold, Niels

Current treatment strategies for multiple myeloma (MM) are highly effective, but most patients develop relapsed/refractory disease (RRMM). The anti-CD38/CD3xCD28 trispecific antibody SAR442257 targets CD38 and CD28 on MM cells and co-stimulates CD3 and CD28 on T cells (TCs). We evaluated different key aspects such as MM cells and T cells avidity interaction, tumor killing, and biomarkers for drug potency in three distinct cohorts of RRMM patients. We found that a significantly higher proportion of RRMM patients (86%) exhibited aberrant co-expression of CD28 compared to newly diagnosed MM (NDMM) patients (19%). Furthermore, SAR442257 mediated significantly higher TC activation, resulting in enhanced MM killing compared to bispecific functional knockout controls for all relapse cohorts (Pearson’s r = 0.7). Finally, patients refractory to anti-CD38 therapy had higher levels of TGF-β (up to 20-fold) compared to other cohorts. This can limit the activity of SAR442257. Vactoserib, a TGF-β inhibitor, was able to mitigate this effect and restore sensitivity to SAR442257 in these experiments. In conclusion, SAR442257 has high potential for enhancing TC cytotoxicity by co-targeting CD38 and CD28 on MM and CD3/CD28 on T cells.

100 项与 anti-CD38/BCMA/CD3 trispecific antibody (Jiangsu hengrui) 相关的药物交易

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