In preclinical models, the use of specific antibodies against vascular endothelial growth factor (VEGF) or VEGFR2 significantly improved the therapeutic efficacy of ex vivo armed T cells (EATs), increasing cytotoxic CD8+ tumor-infiltrating lymphoctytes and high endothelial venules (HEVs) in the tumor microenvironment. The study by Nai-Kong V. Cheung, MD, PhD, of Memorial Sloan Kettering Cancer Center and colleagues was published online in the Journal for ImmunoTherapy of Cancer in March.
The study has “demonstrated the therapeutic potential of VEGF blockade using anti-VEGF or anti-VEGFR2 antibody in combination with tumor-specific EATs,” Cheung and colleagues write. The anti-human VEGF monoclonal antibody bevacizumab and the anti-mouse VEGFR2 antibody DC101 “significantly enhanced intratumoral EAT infiltration and persistence of CD8+ T cells, improving in vivo anti-tumor immune response and survival.”
Abnormal tumor vasculature is a hallmark of most solid tumors and is associated with immune invasion, the authors note. The use of VEGF blockades to normalize tumor vasculature could improve the efficacy of bispecific antibody-based T-cell immunotherapy, they write.
The study’s findings “suggest that both VEGF and VEGFR2 represent attractive targets to improve the antitumor effect of T cell immunotherapy, most likely by vascular normalization and inducing HEVs, increasing CD8(+) T cell survival and dispersion, and mitigating the immunosuppressive TME,” the authors conclude.
- Park JA, Espinosa-Cotton M, Guo HF, Monette S, Cheung NV. Targeting tumor vasculature to improve antitumor activity of T cells armed ex vivo with T cell engaging bispecific antibody. J Immunother Cancer. 2023;11(3):e006680. doi:10.1136/jitc-2023-006680
Tags: bispecific t cell engagers, bite, Immunity, Therapy, BiTEs, therapies, T cells, T cell