{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Krawczyk M"],"funding":["European Research Council","NHLBI NIH HHS"],"pubmed_abstract":["CD19-CAR-T-cells emerge as a major therapeutic option for relapsed/refractory B-cell-derived malignancies, however approximately half of patients eventually relapse. To identify resistance-driving factors, we repeatedly exposed B-cell lymphoma/B-cell acute lymphoblastic leukemia to 4-1BB/CD28-based CD19-CAR-T-cells <i>in vitro</i>. Generated models revealed costimulatory domain-dependent differences in CD19 loss. While CD19-4-1BB-CAR-T-cells induced combination epitope/total CD19 protein loss, CD19-CD28-CAR-T-cells did not drive antigen-escape. Consistent with observations in patients relapsing after CD19-4-1BB-CAR-T-cells, we identified CD19 frameshift/missense mutations affecting residues critical for FMC63 epitope recognition. Mathematical simulations revealed that differences between C"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.02.28.640707"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11908201"],"repository":["biostudies-literature"],"pubmed_title":["The costimulatory domain influences CD19 CAR-T cell resistance development in B-cell malignancies."],"pmcid":["PMC11908201"],"funding_grant_id":["T32 HL007150","805038"],"pubmed_authors":["Winiarski T","Krawczyk M","Walchli S","Benard E","Pepek M","Fernandez-Fuentes N","Davis J","Thomas-Tikhonenko A","Graczyk-Jarzynka A","Menendez P","Puente XS","Fidyt K","Bousquets-Munoz P","Winiarska M"],"additional_accession":[]},"is_claimable":false,"name":"The costimulatory domain influences CD19 CAR-T cell resistance development in B-cell malignancies.","description":"CD19-CAR-T-cells emerge as a major therapeutic option for relapsed/refractory B-cell-derived malignancies, however approximately half of patients eventually relapse. To identify resistance-driving factors, we repeatedly exposed B-cell lymphoma/B-cell acute lymphoblastic leukemia to 4-1BB/CD28-based CD19-CAR-T-cells <i>in vitro</i>. Generated models revealed costimulatory domain-dependent differences in CD19 loss. While CD19-4-1BB-CAR-T-cells induced combination epitope/total CD19 protein loss, CD19-CD28-CAR-T-cells did not drive antigen-escape. Consistent with observations in patients relapsing after CD19-4-1BB-CAR-T-cells, we identified CD19 frameshift/missense mutations affecting residues critical for FMC63 epitope recognition. Mathematical simulations revealed that differences between C","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-04-08T19:50:51.711Z","creation":"2025-04-05T22:10:32.42Z"},"accession":"S-EPMC11908201","cross_references":{"pubmed":["40093096"],"doi":["10.1101/2025.02.28.640707"]}}