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Tumor cells susceptible to OH2 oncolytic infection are malignant cells that possess the specific molecular and physiological characteristics required for the entry and replication of the OH2 oncolytic virus. OH2 is a genetically attenuated Herpes Simplex Virus type 1 (HSV-1) featuring deletions of the ICP34.5 and ICP47 genes, which restrict its replication to cancer cells and enhance immune recognition (PMID: 33028811). The susceptibility of these cells is primarily determined by the surface expression of HSV-1 entry receptors, most notably Nectin-1 (CD111) and Herpesvirus Entry Mediator (HVEM/TNFRSF14) (PMID: 10559355). Furthermore, these cells typically exhibit impaired innate antiviral defenses, such as defective Type I Interferon signaling, which allows the virus to bypass normal cellular safeguards and complete its lytic cycle (PMID: 25403442). Upon infection, OH2 induces direct oncolysis, leading to the release of progeny virions and tumor-associated antigens into the tumor microenvironment. The virus is also engineered to express human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), which promotes the maturation of dendritic cells and the subsequent activation of a systemic, T-cell-mediated anti-tumor immune response (PMID: 32814774). This therapeutic strategy is currently being evaluated in clinical trials for the treatment of various solid tumors, including melanoma and gastrointestinal malignancies.
Selective viral replication in tumor cells leading to direct oncolysis and induction of systemic anti-tumor immunity via GM-CSF expression.
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