biostudies-literatureSugita MNIA NIH HHSNCI NIH HHS305https://www.ebi.ac.uk/biostudies/studies/S-EPMC10160073biostudies-literatureUnknown14(5)Autologous T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19 are approved for the treatment of various CD19⁺ hematological malignancies. While CAR T cells induce objective responses in a majority of patients, relapse frequently occurs upon loss of CD19 expression by neoplastic cells. Radiation therapy (RT) has been successfully employed to circumvent the loss of CAR targets in preclinical models of pancreatic cancer. At least in part, this reflects the ability of RT to elicit death receptor (DR) expression by malignant cells, enabling at least some degree of CAR-independent tumor killing. In a human model of CD19⁺ acute lymphoblastic leukemia (ALL), we also observed DR upregulation by RT, both in vitro and in vivo. Moreover, low-dose toCell death & diseaseRadiation therapy improves CAR T cell activity in acute lymphoblastic leukemia.PMC10160073R01 CA098571U54 CA274291R21 AG066552R21 CA245454R01 CA234478Latouche JBVan Besien KSugita MAlhomoud MBoyer OGuzman MLFormenti SCGalluzzi LMartinet JGolden EYamazaki TfalseRadiation therapy improves CAR T cell activity in acute lymphoblastic leukemia.Autologous T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19 are approved for the treatment of various CD19⁺ hematological malignancies. While CAR T cells induce objective responses in a majority of patients, relapse frequently occurs upon loss of CD19 expression by neoplastic cells. Radiation therapy (RT) has been successfully employed to circumvent the loss of CAR targets in preclinical models of pancreatic cancer. At least in part, this reflects the ability of RT to elicit death receptor (DR) expression by malignant cells, enabling at least some degree of CAR-independent tumor killing. In a human model of CD19⁺ acute lymphoblastic leukemia (ALL), we also observed DR upregulation by RT, both in vitro and in vivo. Moreover, low-dose to2023-01-01T00:00:00Z2023 May2025-04-22T00:31:16.837Z2025-04-05T19:36:59.351ZS-EPMC101600733714256810.1038/s41419-023-05829-6