Acquired resistance to a GPRC5D-directed T-cell engager in multiple myeloma is mediated by genetic or epigenetic target inactivation - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Cancer Année : 2023

Acquired resistance to a GPRC5D-directed T-cell engager in multiple myeloma is mediated by genetic or epigenetic target inactivation

Résumé

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. Molecular profiling of target genes may help to guide the choice of immunotherapy and early detection of resistance in multiple myeloma.
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hal-04265728 , version 1 (06-11-2023)

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Jennifer Derrien, Sarah Gastineau, Antoine Frigout, Nils Giordano, Mia Cherkaoui, et al.. Acquired resistance to a GPRC5D-directed T-cell engager in multiple myeloma is mediated by genetic or epigenetic target inactivation. Nature Cancer, In press, ⟨10.1038/s43018-023-00625-9⟩. ⟨hal-04265728⟩
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