{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Coffey DG"],"funding":["NCI NIH HHS"],"pagination":["220-233"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11738034"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["145(2)"],"pubmed_abstract":["<h4>Abstract</h4>Chimeric antigen receptor (CAR) T cells and bispecific antibodies targeting B-cell maturation antigen (BCMA) have significantly advanced the treatment of relapsed and refractory multiple myeloma. Resistance to BCMA-targeting therapies, nonetheless, remains a significant challenge. BCMA shedding by γ-secretase is a known resistance mechanism, and preclinical studies suggest that inhibition may improve anti-BCMA therapy. Leveraging a phase 1 clinical trial of the γ-secretase inhibitor (GSI), crenigacestat, with anti-BCMA CAR T cells (FCARH143), we used single-nuclei RNA sequencing and assay for transposase-accessible chromatin sequencing to characterize the effects of GSI on the tumor microenvironment. The most significant impacts of GSI involved effects on monocytes, which "],"journal":["Blood"],"pubmed_title":["Single-cell analysis of the multiple myeloma microenvironment after γ-secretase inhibition and CAR T-cell therapy."],"pmcid":["PMC11738034"],"funding_grant_id":["P01 CA018029"],"pubmed_authors":["Atilla E","Comstock ML","Green DJ","Pont MJ","Riddell SR","Landgren O","Hill GR","Ataca Atilla P","Cowan AJ","Coffey DG","Simon S"],"additional_accession":[]},"is_claimable":false,"name":"Single-cell analysis of the multiple myeloma microenvironment after γ-secretase inhibition and CAR T-cell therapy.","description":"<h4>Abstract</h4>Chimeric antigen receptor (CAR) T cells and bispecific antibodies targeting B-cell maturation antigen (BCMA) have significantly advanced the treatment of relapsed and refractory multiple myeloma. Resistance to BCMA-targeting therapies, nonetheless, remains a significant challenge. BCMA shedding by γ-secretase is a known resistance mechanism, and preclinical studies suggest that inhibition may improve anti-BCMA therapy. Leveraging a phase 1 clinical trial of the γ-secretase inhibitor (GSI), crenigacestat, with anti-BCMA CAR T cells (FCARH143), we used single-nuclei RNA sequencing and assay for transposase-accessible chromatin sequencing to characterize the effects of GSI on the tumor microenvironment. The most significant impacts of GSI involved effects on monocytes, which ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-06-01T17:54:33.355Z","creation":"2026-04-08T14:25:11.471Z"},"accession":"S-EPMC11738034","cross_references":{"pubmed":["39374522"],"doi":["10.1182/blood.2024025231"]}}