Cellular entry receptors and tumor-associated determinants

Cellular entry receptors and tumor-associated determinants is a descriptive term used in pharmacological databases to categorize the complex mechanism of action for oncolytic viruses, most notably Pelareorep (Reolysin). Pelareorep is an isolate of the mammalian orthoreovirus type 3 Dearing that selectively infects and lyses malignant cells. The virus utilizes Junctional Adhesion Molecule A (JAM-A) as its primary high-affinity entry receptor and sialic acid as a low-affinity co-receptor (Barton et al., 2001, Cell; Reiter et al., 2011, J Virol). The 'tumor-associated determinants' refer to the intracellular environment, specifically an activated Ras signaling pathway; in normal cells, Protein Kinase R (PKR) prevents viral replication, but in Ras-activated cancer cells, PKR is inhibited, allowing the virus to replicate and cause oncolysis (Strong et al., 1998, EMBO J). This selective process leads to direct tumor cell death and the subsequent release of viral progeny and tumor antigens, which can trigger a systemic anti-tumor immune response.

Other names

Unknown cellular entry receptors and tumor-associated determinantsPelareorep targetsReovirus entry receptorsJAM-A and Ras pathway

Selective oncolytic viral replication and induction of anti-tumor immunity