{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Appelbaum J"],"funding":["American Society of Hematology","NCI NIH HHS"],"pagination":["e162593"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11060733"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["134(9)"],"pubmed_abstract":["Chimeric antigen receptor (CAR) designs that incorporate pharmacologic control are desirable; however, designs suitable for clinical translation are needed. We designed a fully human, rapamycin-regulated drug product for targeting CD33+ tumors called dimerizaing agent-regulated immunoreceptor complex (DARIC33). T cell products demonstrated target-specific and rapamycin-dependent cytokine release, transcriptional responses, cytotoxicity, and in vivo antileukemic activity in the presence of as little as 1 nM rapamycin. Rapamycin withdrawal paused DARIC33-stimulated T cell effector functions, which were restored following reexposure to rapamycin, demonstrating reversible effector function control. While rapamycin-regulated DARIC33 T cells were highly sensitive to target antigen, CD34+ stem ce"],"journal":["The Journal of clinical investigation"],"pubmed_title":["Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing."],"pmcid":["PMC11060733"],"funding_grant_id":["ASH Scholar","K12 CA076930"],"pubmed_authors":["Crago W","Zak DE","Martin U","Leonardi M","Sanabria A","Zhang J","Eckelman B","Jensen MC","Price AE","Appelbaum J","Hilton SK","Timmer J","Leung WH","Jarjour J","Sarkar S","Woodworth J","Bilic S","Xia D","Fitzgerald M","Logan R","So PP","Ngwenyama N","Evandy C","Krostag AR","Lewis P","Lamble A","Pogson M","Tampella G","Franke-Welch S","Astrakhan A","Tulberg N","Hollands A","Gregory PD","Jones K","Rawlings-Rhea S","Gardner RA","Gustafson JA","Oda K"],"additional_accession":[]},"is_claimable":false,"name":"Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.","description":"Chimeric antigen receptor (CAR) designs that incorporate pharmacologic control are desirable; however, designs suitable for clinical translation are needed. We designed a fully human, rapamycin-regulated drug product for targeting CD33+ tumors called dimerizaing agent-regulated immunoreceptor complex (DARIC33). T cell products demonstrated target-specific and rapamycin-dependent cytokine release, transcriptional responses, cytotoxicity, and in vivo antileukemic activity in the presence of as little as 1 nM rapamycin. Rapamycin withdrawal paused DARIC33-stimulated T cell effector functions, which were restored following reexposure to rapamycin, demonstrating reversible effector function control. While rapamycin-regulated DARIC33 T cells were highly sensitive to target antigen, CD34+ stem ce","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-03-31T10:54:48.653Z","creation":"2025-08-30T03:05:49.518Z"},"accession":"S-EPMC11060733","cross_references":{"pubmed":["38502193"],"doi":["10.1172/JCI162593"]}}