Tumor cell entry receptors exploited by CF33 (GAGs)

Tumor cell entry receptors exploited by CF33 refer to the cell surface molecules that facilitate the attachment and internalization of the chimeric oncolytic orthopoxvirus CF33 into malignant cells. Unlike many oncolytic viruses that require specific, often overexpressed protein receptors (such as Nectin-1 for HSV or CAR for Adenovirus), CF33 primarily utilizes ubiquitously expressed glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate, for initial attachment. This broad tropism allows CF33 to infect a wide range of solid tumors regardless of their specific protein receptor profiles, making it a versatile tool for treating heterogeneous malignancies. Additionally, CF33 can exploit the scavenger receptor MARCO, which is frequently expressed on tumor-associated macrophages and myeloid-derived suppressor cells, potentially enhancing its ability to modulate the tumor microenvironment. Following attachment, the virus enters cells through direct membrane fusion or macropinocytosis, a process that can be facilitated by host signaling pathways such as those involving the epidermal growth factor receptor (EGFR). The therapeutic selectivity of CF33 is further refined by intracellular mechanisms, such as the deletion of the thymidine kinase (TK) gene, which restricts viral replication to rapidly dividing cancer cells.

Other names

Heparan sulfate proteoglycans (HSPGs)Chondroitin sulfate proteoglycans (CSPGs)Glycosaminoglycans (GAGs)MARCO (Macrophage receptor with collagenous structure)Scavenger receptor MARCO

Viral attachment to glycosaminoglycans and MARCO followed by membrane fusion or macropinocytosis to initiate oncolysis and immunogenic cell death.