Oncolytic virus-sensitive tumor cell

Oncolytic virotherapy targets tumor cells by exploiting specific phenotypic alterations that distinguish them from healthy tissue. This selectivity is primarily driven by the overexpression of viral entry receptors—such as Nectin-1 for herpes simplex virus or CD155 for poliovirus—and the presence of defective innate antiviral pathways, particularly the Type I interferon (IFN) response (Lichty et al., 2014). While normal cells can sense viral double-stranded RNA and initiate a signaling cascade involving PKR and IRF3 to halt protein synthesis and induce apoptosis, many cancers lose these defenses to avoid immune surveillance (Xia et al., 2014). Consequently, oncolytic viruses can selectively replicate within these permissive tumor cells, leading to direct cellular lysis. This process, known as oncolysis, releases progeny virions, damage-associated molecular patterns (DAMPs), and tumor-associated antigens (TAAs) into the microenvironment. These factors collectively stimulate a systemic, T-cell-mediated anti-tumor immune response, effectively turning the tumor into an in situ vaccine (Kaufman et al., 2015). Therapeutic agents like Talimogene laherparepvec (T-VEC) utilize these mechanisms to treat advanced malignancies like melanoma (Bommareddy et al., 2018). The success of this approach depends on the density of entry receptors and the degree of antiviral signaling impairment within the target cell population.

Other names

Oncolytic virus targetPermissive tumor cellIFN-deficient cancer cellVirotherapy-susceptible tumor cell

Selective viral replication within tumor cells leading to direct cell lysis and induction of systemic anti-tumor immunity.