Data from Armored Chimeric Antigen Receptor T-cell Therapy Targets Antigen-Heterogeneous Glioma

<jats:p>&lt;div&gt;Abstract &lt;p&gt;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 &lt;i&gt;in vivo&lt;/i&gt; 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.&lt;/p&gt; Significance:&lt;p&gt;CAR-T cells armored with cytokines and anti-VEGF single-chain variable fragments can control orthotopic, antigen-heterogeneous glioma with minimal toxicity, providing a therapeutic strategy for glioblastoma patients in urgent need of efficacious treatments.&lt;/p&gt;&lt;/div&gt;</jats:p>