ArticleScience advances2026
Antigen spreading mediates heterogeneous solid tumor eradication by DNA demethylating agent-programmed CAR T cells.
Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
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Abstract
Antigen heterogeneity substantially limits the efficacy of chimeric antigen receptor-modified T (CAR T) cell therapy against solid tumors. Our study highlights the potent antitumor activity of low-dose decitabine-primed CAR T (dCAR T) cells in solid tumor models, a benefit previously confirmed in hematologic malignancies. Notably, dCAR T cell infusion in immunocompetent mice led to substantial elimination of mixed tumor masses containing both antigen-positive and antigen-negative cells, without the need for prior lymphodepletion. Our analysis showed notable proinflammatory remodeling of the tumor immunosuppressive microenvironment. Crucially, antigen-activated dCAR T cells sustained high levels of interferon-γ production, which induced immunogenic cell death in tumor cells and activated conventional dendritic cells. This, in turn, stimulated endogenous CD8
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