SAR-442257 is a trispecific T-cell engager and monoclonal antibody that binds to CD38, CD3 and CD28. SAR-442257 can target and bind to CD3 and CD28 on T cells, as well as CD38 expressed on tumor cells. SAR-442257 mediates T-cell activation, enhances T-cell activity, induces T-cell degranulation, and drives cytotoxicity against multiple myeloma cells. SAR-442257 functions via CD38 expression, and its in vitro activity correlates with CD38 expression on the surface of multiple myeloma cells. SAR-442257 can be used in studies related to multiple myeloma and relapsed/refractory multiple myeloma [1] [2].
In Vivo, SAR442257 suppresses myeloma growth in a humanized mouse model[2]. SAR442257 stimulates memory/effector T cell proliferation, reduces regulatory T cells, and is well-tolerated in non-human primates[2].
In Vitro, SAR-442257 (0.001-10 nM; 48 h) potently reduces primary multiple myeloma cell viability ex vivo with picomolar EC50 valuesl[1]. SAR-442257 (1 nM; 48 h) induces significant degranulation of endogenous CD3+ T cells in bone marrow mononuclear cells (MNCs) derived from multiple myeloma samples[1]. SAR-442257 (1 nM; 48 h)-mediated cytotoxicity against primary multiple myeloma cells is dependent on the presence of endogenous CD3+ T cells[1]. SAR-442257 (1 nM; 48 h) response in primary multiple myeloma samples has surface CD38 expression (6-fold higher MFI on multiple myeloma cells vs. non-myeloma cells) as the strongest biomarker, while a very low E:T ratio may contribute to resistance[1]. SAR-442257 (1 nM, 10 nM, 100 nM, 1000 nM; 7.5 min) enhances T cell-to-multiple myeloma cell binding avidity, inducing a 1.5-fold higher frequency of bound T cells in U266 and MM1S cell lines compared to the CD38-CD3 bispecific antibody[2]. SAR-442257 (0.01-16 nM; 24 h) potently induces dose-dependent cytotoxicity against 10 human multiple myeloma cell lines, with EC50 values of 0.02 nM (MM1S) and 0.2 nM (U266), and reduces cell viability by 58-97% at 1 nM after 24 h[2].
References:
[1]. Keller AL, et al. Ex Vivo Efficacy of SAR442257 Anti-CD38 Trispecific T-cell Engager in Multiple Myeloma Relapsed After Daratumumab and BCMA-targeted Therapies. Cancer research communications. 2024 Mar 12;4(3):757-764.
[2]. Grab AL, et al. Pre-Clinical Assessment of SAR442257, a CD38/CD3xCD28 Trispecific T Cell Engager in Treatment of Relapsed/Refractory Multiple Myeloma. Cells. 2024 May 20;13(10):879.
In Vivo, SAR442257 suppresses myeloma growth in a humanized mouse model[2]. SAR442257 stimulates memory/effector T cell proliferation, reduces regulatory T cells, and is well-tolerated in non-human primates[2].
In Vitro, SAR-442257 (0.001-10 nM; 48 h) potently reduces primary multiple myeloma cell viability ex vivo with picomolar EC50 valuesl[1]. SAR-442257 (1 nM; 48 h) induces significant degranulation of endogenous CD3+ T cells in bone marrow mononuclear cells (MNCs) derived from multiple myeloma samples[1]. SAR-442257 (1 nM; 48 h)-mediated cytotoxicity against primary multiple myeloma cells is dependent on the presence of endogenous CD3+ T cells[1]. SAR-442257 (1 nM; 48 h) response in primary multiple myeloma samples has surface CD38 expression (6-fold higher MFI on multiple myeloma cells vs. non-myeloma cells) as the strongest biomarker, while a very low E:T ratio may contribute to resistance[1]. SAR-442257 (1 nM, 10 nM, 100 nM, 1000 nM; 7.5 min) enhances T cell-to-multiple myeloma cell binding avidity, inducing a 1.5-fold higher frequency of bound T cells in U266 and MM1S cell lines compared to the CD38-CD3 bispecific antibody[2]. SAR-442257 (0.01-16 nM; 24 h) potently induces dose-dependent cytotoxicity against 10 human multiple myeloma cell lines, with EC50 values of 0.02 nM (MM1S) and 0.2 nM (U266), and reduces cell viability by 58-97% at 1 nM after 24 h[2].
References:
[1]. Keller AL, et al. Ex Vivo Efficacy of SAR442257 Anti-CD38 Trispecific T-cell Engager in Multiple Myeloma Relapsed After Daratumumab and BCMA-targeted Therapies. Cancer research communications. 2024 Mar 12;4(3):757-764.
[2]. Grab AL, et al. Pre-Clinical Assessment of SAR442257, a CD38/CD3xCD28 Trispecific T Cell Engager in Treatment of Relapsed/Refractory Multiple Myeloma. Cells. 2024 May 20;13(10):879.