biostudies-literatureCai WAll of Us Research Program (Precision Medicine Initiative Cohort Program)Geoffrey Beene Cancer Research CenterAll of Us Research ProgramCenter for Experimental Therapeutic of MSKNCI NIH HHSEdward P. Evans Foundation1361-1379https://www.ebi.ac.uk/biostudies/studies/S-EPMC11444887biostudies-literatureUnknown12(10)Chimeric antigen receptor (CAR) T-cell therapy has resulted in remarkable clinical success in the treatment of B-cell malignancies. However, its clinical efficacy in solid tumors is limited, primarily by target antigen heterogeneity. To overcome antigen heterogeneity, we developed CAR T cells that overexpress LIGHT, a ligand of both lymphotoxin-β receptor on cancer cells and herpes virus entry mediator on immune cells. LIGHT-expressing CAR T cells displayed both antigen-directed cytotoxicity mediated by the CAR and antigen-independent killing mediated through the interaction of LIGHT with lymphotoxin-β receptor on cancer cells. Moreover, CAR T cells expressing LIGHT had immunostimulatory properties that improved the cells' proliferation and cytolytic profile. These data indicate that LIGHTCancer immunology researchAugmenting CAR T-cell Functions with LIGHT.PMC11444887P30 CA008748P50 CA254838-01P50 CA254838R35 CA5241894P30 CA08748-40R35 CA2418941818119291Brentjens RJPurdon TJKhan JFSouness SHealey JHScheinberg DAMeyerberg JRahman JFujino Tde Stanchina ERajasekhar VKMi XAbrahimi PDaniyan AFYoo SMcDowell JRTanaka KCai WMathew SAbdel-Wahab OfalseAugmenting CAR T-cell Functions with LIGHT.Chimeric antigen receptor (CAR) T-cell therapy has resulted in remarkable clinical success in the treatment of B-cell malignancies. However, its clinical efficacy in solid tumors is limited, primarily by target antigen heterogeneity. To overcome antigen heterogeneity, we developed CAR T cells that overexpress LIGHT, a ligand of both lymphotoxin-β receptor on cancer cells and herpes virus entry mediator on immune cells. LIGHT-expressing CAR T cells displayed both antigen-directed cytotoxicity mediated by the CAR and antigen-independent killing mediated through the interaction of LIGHT with lymphotoxin-β receptor on cancer cells. Moreover, CAR T cells expressing LIGHT had immunostimulatory properties that improved the cells' proliferation and cytolytic profile. These data indicate that LIGHT2024-01-01T00:00:00Z2024 Oct2026-06-01T06:07:47.381Z2026-04-08T09:53:24.89ZS-EPMC114448873895933710.1158/2326-6066.CIR-24-024610.1158/2326-6066.cir-24-0246