Engineering CAR T cells to secrete VEGF-neutralizing scFvs enhances antitumor activity against solid tumors - PubMed
4 hours ago
- #VEGF
- #solid tumors
- #CAR T cells
- CAR T cell therapy has limited efficacy against solid tumors due to immunosuppressive tumor microenvironments (TMEs).
- TMEs often have high levels of vascular endothelial growth factor A (VEGF), contributing to immunosuppression and abnormal tumor vasculature.
- CAR T cells engineered to secrete anti-VEGF single-chain variable fragments (CAR-αVEGF T cells) showed superior antitumor efficacy in ovarian cancer and glioma models.
- CAR-αVEGF T cells outperformed conventional CAR T cells, even when combined with anti-VEGF antibody therapy.
- These engineered T cells exhibited enhanced activation, mitochondrial fitness, and immune-stimulatory signatures in the tumor-bearing brain.
- CAR-αVEGF T cells mitigated negative effects like suppressive myeloid cell infiltration, abnormal vasculature, and hypoxia.
- The findings support clinical translation of CAR-αVEGF T cells for solid tumors with elevated VEGF.