التفاصيل البيبلوغرافية
| العنوان: |
Pre-Clinical Assessment of SAR442257, a CD38/CD3xCD28 Trispecific T Cell Engager in Treatment of Relapsed/Refractory Multiple Myeloma. |
| المؤلفون: |
Grab, Anna Luise, Kim, Peter S., John, Lukas, Bisht, Kamlesh, Wang, Hongfang, Baumann, Anja, Van de Velde, Helgi, Sarkar, Irene, Shome, Debarati, Reichert, Philipp, Manta, Calin, Gryzik, Stefanie, Reijmers, Rogier M., Weinhold, Niels, Raab, Marc S. |
| المصدر: |
Cells (2073-4409); May2024, Vol. 13 Issue 10, p879, 17p |
| مصطلحات موضوعية: |
MULTIPLE myeloma, T cells, RITUXIMAB, CD28 antigen, CD38 antigen, CYTOTOXINS, CD3 antigen |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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