Target intelligence / Profile preview

Tumor cells susceptible to OH2 oncolytic infection

Molecular classification
Other
01

Overview

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.

Other names
OH2-susceptible tumor cellsHSV-1 susceptible cancer cellsVOH2-susceptible cells
02

Mechanism of action

Selective viral replication in tumor cells leading to direct oncolysis and induction of systemic anti-tumor immunity via GM-CSF expression.

03

Biological functions

Cell deathImmune responseViral replication
04

Disease associations

Cancer
05

Safety considerations

Off-target viral infectionNeutralizing antiviral antibodiesCytokine release syndromeViral shedding
06

Interacting drugs

OH2 (Oncolytic Herpes Simplex Virus type 1)

1 more in the full profile.

07

Biomarkers

Nectin-1 (CD111) expressionHerpesvirus entry mediator (HVEM) expressionType I Interferon signaling deficiency

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