biostudies-literatureAndo MMEXT | Japan Society for the Promotion of ScienceJapan Agency for Medical Research and Development41-55https://www.ebi.ac.uk/biostudies/studies/S-EPMC9973402biostudies-literatureUnknown1(1)T cells with a stem cell memory (T_SCM) phenotype provide long-term and potent antitumor effects for T-cell transfer therapies. Although various methods for the induction of T_SCM-like cells <i>in vitro</i> have been reported, few methods generate T_SCM-like cells from effector/exhausted T cells. We have reported that coculture with the Notch ligand-expressing OP9 stromal cells induces T_SCM-like (iT_SCM) cells. Here, we established a feeder-free culture system to improve iT_SCM cell generation from expanded chimeric antigen receptor (CAR)-expressing T cells; culturing CAR T cells in the presence of IL7, CXCL12, IGF-I, and the Notch ligand, hDLL1. Feeder-free CAR-iT_SCM cells showed the expression of cell surface markersCancer research communicationsRejuvenating Effector/Exhausted CAR T Cells to Stem Cell Memory-Like CAR T Cells By Resting Them in the Presence of CXCL12 and the NOTCH Ligand.PMC997340221H0271921H0504420gm621001220gm111000921zf0127003h000117H06175Shichino SYoshimura AKondo TSrirat TTomisato WIto MMise-Omata SAndo MNakagawara KfalseRejuvenating Effector/Exhausted CAR T Cells to Stem Cell Memory-Like CAR T Cells By Resting Them in the Presence of CXCL12 and the NOTCH Ligand.T cells with a stem cell memory (T_SCM) phenotype provide long-term and potent antitumor effects for T-cell transfer therapies. Although various methods for the induction of T_SCM-like cells <i>in vitro</i> have been reported, few methods generate T_SCM-like cells from effector/exhausted T cells. We have reported that coculture with the Notch ligand-expressing OP9 stromal cells induces T_SCM-like (iT_SCM) cells. Here, we established a feeder-free culture system to improve iT_SCM cell generation from expanded chimeric antigen receptor (CAR)-expressing T cells; culturing CAR T cells in the presence of IL7, CXCL12, IGF-I, and the Notch ligand, hDLL1. Feeder-free CAR-iT_SCM cells showed the expression of cell surface markers2021-01-01T00:00:00Z2021 Oct2026-05-28T17:56:47.62Z2024-12-03T15:58:58.327ZS-EPMC99734023686091110.1158/2767-9764.CRC-21-0034