biostudies-literatureAppelbaum JAmerican Society of HematologyNCI NIH HHSe162593https://www.ebi.ac.uk/biostudies/studies/S-EPMC11060733biostudies-literatureUnknown134(9)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 ceThe Journal of clinical investigationDrug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.PMC11060733ASH ScholarK12 CA076930Crago WZak DEMartin ULeonardi MSanabria AZhang JEckelman BJensen MCPrice AEAppelbaum JHilton SKTimmer JLeung WHJarjour JSarkar SWoodworth JBilic SXia DFitzgerald MLogan RSo PPNgwenyama NEvandy CKrostag ARLewis PLamble APogson MTampella GFranke-Welch SAstrakhan ATulberg NHollands AGregory PDJones KRawlings-Rhea SGardner RAGustafson JAOda KfalseDrug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.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 ce2024-01-01T00:00:00Z2024 Mar2026-03-31T10:54:48.653Z2025-08-30T03:05:49.518ZS-EPMC110607333850219310.1172/JCI162593