Tumor cells permissive to pelareorep replication

Tumor cells permissive to pelareorep replication are defined by a cellular environment, typically driven by an activated Ras signaling pathway, that allows the mammalian orthoreovirus type 3 Dearing strain (pelareorep) to complete its life cycle. In healthy cells, the double-stranded RNA-activated protein kinase (PKR) pathway acts as a sentinel, detecting viral dsRNA and halting protein translation to prevent viral spread. However, in many cancers, aberrant Ras signaling or downstream mutations inhibit PKR, rendering these cells uniquely susceptible to reovirus infection (Gong et al., 2016, Front Oncol). Once the virus infects these permissive cells, it hijacks the host machinery to produce progeny virions, eventually leading to cell lysis and the release of tumor-associated antigens. This direct oncolytic effect is complemented by the induction of a 'hot' tumor microenvironment, which recruits and activates T cells to target the malignancy (Mahalingam et al., 2020, Cancers). Consequently, the permissiveness of these cells is the fundamental requirement for the therapeutic efficacy of pelareorep in treating various solid and hematological tumors.

Other names

Ras-activated tumor cellsReovirus-permissive cellsPelareorep-sensitive tumor cellsReolysin-permissive cells

Pelareorep, an oncolytic reovirus, selectively replicates in tumor cells with an activated Ras signaling pathway. In normal cells, viral double-stranded RNA (dsRNA) activates protein kinase R (PKR), which phosphorylates eIF-2alpha to inhibit viral protein synthesis. In Ras-activated tumor cells, PKR activation is suppressed, allowing the virus to replicate, cause direct oncolysis, and stimulate a systemic anti-tumor immune response (Coffey et al., 1998, Science; Strong et al., 1998, EMBO J).