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Enadenotucirev (formerly ColoAd1) is a chimeric oncolytic adenovirus (Ad11p/Ad3) that selectively targets and kills cancer cells. Its entry into tumor cells is primarily mediated by two cell-surface receptors: Membrane cofactor protein (CD46) and Desmoglein 2 (DSG2). CD46 is a complement regulatory protein that protects host cells from complement-mediated damage, while DSG2 is a component of desmosomes involved in cell-cell adhesion. Both receptors are frequently overexpressed in various carcinomas, including colorectal, lung, and ovarian cancers, which facilitates the preferential uptake of enadenotucirev by malignant tissues. Upon binding to these receptors, the virus is internalized, leading to selective viral replication and subsequent oncolysis, which releases tumor antigens and stimulates an anti-tumor immune response. The use of these receptors, particularly CD46, allows enadenotucirev to be delivered systemically (intravenously) with reduced neutralization by blood components compared to traditional Ad5-based vectors.
Enadenotucirev binds to CD46 and Desmoglein 2 on the tumor cell surface to facilitate viral attachment and internalization, leading to selective replication and oncolysis.
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