Abstract 7286: A first-in-class αPD-1/αVEGF/IL-2v tri-specific fusion protein demonstrates promising anti-tumor efficacy in immune checkpoint inhibitor-resistant tumor models
Abstract
Immune checkpoint inhibitors (ICIs), including anti-PD(L)1 monoclonal antibodies, have been widely approved and used for various cancer types. However, the response rate to ICIs is limited to certain cancer types, largely attributed to the absence or low presence of immune cells within the tumor microenvironment (TME). αVEGF antibodies not only facilitate immune cell infiltration into tumors but also improve the immunosuppressive conditions of the TME. Notably, the combination of αPD-1 and αVEGF antibodies and αPD-1/αVEGF bispecific antibody therapy have demonstrated improved efficacy compared to αPD-1 monotherapy across various cancer types. Despite such advances, boosting immune cell proliferation within the TME remains crucial for achieving superior efficacy in ICI-resistant or refractory patients. αPD-1/αVEGF/IL-2v is a highly TME-selective tri-specific fusion protein comprising αPD-1, αVEGF, and IL-2v. This compound was engineered to activate T cells continuously via αPD-1, enhance tumor-infiltrating lymphocytes (TILs) via αVEGF, and proliferate effector T cells strongly via novel IL-2v. We evaluated the intrinsic activity of each functional arm of the αPD-1/αVEGF/IL-2v fusion protein individually. The αPD-1/αVEGF/IL-2v exhibited blocking activity against PD-1/PD-L1 binding comparable to pembrolizumab, showed VEGF/VEGFR blockade activity similar to that of αVEGF antibody, and effectively induced CD8+ T cell activation comparable to aldesleukin. In vitro…
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