Integrin alpha-V beta-3 and alpha-V beta-5 (alphaVbeta3/alphaVbeta5)

Integrin alpha-V beta-3 and alpha-V beta-5 are heterodimeric cell-surface receptors that play a pivotal role in mediating cell-to-extracellular matrix adhesion and intracellular signaling (UniProt, 2024). These integrins are frequently overexpressed in various solid tumors and the associated angiogenic vasculature, making them ideal targets for selective therapeutic delivery (Martinez-Quintanilla et al., 2015). In the context of VCN-12, an oncolytic adenovirus, these integrins serve as the primary receptors for viral attachment and entry (Theriva Biologics, 2024). VCN-12 is engineered with an RGD (Arg-Gly-Asp) motif in its fiber protein, which specifically recognizes and binds to these integrins with high affinity (Cousin et al., 2017). This interaction allows the virus to bypass the Coxsackievirus and Adenovirus Receptor (CAR), which is often downregulated in advanced cancers, thereby ensuring efficient infection of tumor cells (Garcia-Carbonero et al., 2022). Once bound, the virus is internalized, leading to tumor-selective replication, oncolysis, and the release of therapeutic payloads such as hyaluronidase and anti-PD-L1 antibodies into the tumor microenvironment (Theriva Biologics, 2024). This dual-targeting and payload delivery approach aims to overcome the physical and immunological barriers of the tumor stroma.

Other names

Vitronectin receptorCD51/CD61ITGAV/ITGB3ITGAV/ITGB5RGD-binding integrinsTumor cell-surface integrins mediating VCN-12 attachment and entry

VCN-12 utilizes an RGD (Arg-Gly-Asp) motif engineered into the HI-loop of its fiber knob to bind with high affinity to alpha-V beta-3 and alpha-V beta-5 integrins on the tumor cell surface (Cousin et al., 2017; Theriva Biologics, 2024). This binding triggers receptor-mediated endocytosis, allowing the viral capsid to enter the host cell and initiate the lytic cycle (Martinez-Quintanilla et al., 2015).