Product Description
CPB514 is a 2+2 symmetric tetravalent bispecific engineered to simultaneously target mouse programmed death-ligand 1 (PD-L1, CD274, B7-H1) and mouse vascular endothelial growth factor A (VEGF-A), integrating checkpoint inhibition and anti-angiogenesis into a single molecule. CPB514 contains the murine IgG2a constant region to reduce immunogenicity and the formation of anti-drug antibodies (ADAs) in mouse models and LALA-PG Fc-silencing mutations to abolish antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) while minimizing Fc-driven off-target toxicity and focusing the mechanism on checkpoint/angiogenesis blockade rather than target-cell depletion. The PD-L1 arm binds tumor and myeloid PD-L1 to prevent interaction with PD-1 on T cells, restoring TCR signaling, NFAT activation, proliferation and cytotoxic function of effector T cells. The VEGF arm sequesters VEGF-A, preventing engagement of VEGFR1/2 on endothelial cells and inhibits downstream PI3K-AKT-mTOR and related pathways that drive angiogenesis, vascular permeability and tumor growth. Relieving PD-1/PD-L1-mediated immunosuppression and blocking VEGF-driven angiogenesis with cooperative binding can enrich bispecific molecules within VEGF/PD-L1-rich tumor microenvironments. This dual targeting can localize anti-VEGF activity to PD-L1-expressing tumor sites while enhancing T-cell activation and vascular normalization.
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