Publications by authors named "S Minvielle"
Bispecific T-cell engagers (TCEs) are revolutionizing patient care in multiple myeloma (MM). These monoclonal antibodies, that redirect T cells against cancer cells, are now approved for the treatment of triple-class exposed relapsed/refractory MM (RRMM). They are currently tested in earlier lines of the disease, including in first line.
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- Researchers used CRISPR/Cas9 to create TP53-/- clones from human myeloma cell lines to study p53-dependent gene expression, identifying a functional score based on 13 genes downregulated when p53 is silenced.
- This score can differentiate myeloma cells based on TP53 status, predict patient survival, and identifies patients with complete TP53 inactivation.
- The study found that the p53-regulated gene BAX impacts myeloma cell sensitivity to specific treatments, and combining MCL1 and BCL2 inhibitors may provide better treatment options for patients with TP53 inactivation.
Bispecific antibodies targeting GPRC5D demonstrated promising efficacy in multiple myeloma, but acquired resistance usually occurs within a few months. Using a single-nucleus multi-omic strategy in three patients from the MYRACLE cohort (ClinicalTrials.gov registration: NCT03807128 ), we identified two resistance mechanisms, by bi-allelic genetic inactivation of GPRC5D or by long-range epigenetic silencing of its promoter and enhancer regions.
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