Armored Chimeric Antigen Receptor T-cell Therapy Targets Antigen-Heterogeneous Glioma
Menée à l'aide notamment d'un modèle murin de gliome à hétérogénéité antigénique, cette étude met en évidence l'intérêt thérapeutique de lymphocytes CAR-T sécrétant certaines cytokines (Interleukine IL-12 et interleukine IL-18 modifiée)
Chimeric antigen receptor (CAR) T-cell therapy has shown early promise against glioblastoma, which lacks effective treatment options. However, two key challenges curtail efficacy: tumor-antigen heterogeneity and an immunosuppressive tumor microenvironment. CAR T cells engineered to secrete combinations of immunomodulatory proteins can reverse immune suppression and engage endogenous immunity. Through head-to-head in vivo comparisons of potentially synergistic armor combinations, we demonstrated that T cells expressing a CAR plus IL12 and the decoy-resistant form of IL18 (CAR-12.DR18 T cells) show strong efficacy against antigen-heterogeneous glioma in immunocompetent mice. Robust antitumor efficacy with effective toxicity mitigation was achieved via combined administration of CAR-12.DR18 T cells with CAR T cells that secrete an anti–vascular endothelial growth factor (anti-VEGF) single-chain variable fragment (scFv). This combination therapy presents a clinically applicable strategy to overcome key barriers to the effective treatment of glioblastoma.
Cancer Research , résumé, 2026