Tumor cells expressing HSV-1 entry receptors with impaired antiviral responses

This target refers to a specific subset of malignant cells characterized by the presence of surface receptors required for Herpes Simplex Virus type 1 (HSV-1) entry, such as Nectin-1 (CD111) or HVEM (TNFRSF14), combined with a compromised innate antiviral defense system [Campadelli-Fiume et al., 2007]. In healthy cells, the detection of viral components triggers the production of Type I interferons (IFNs) and the activation of pathways like PKR, which halt protein synthesis and prevent viral spread. Many tumor cells harbor mutations or epigenetic silencing in these pathways (e.g., STING or IRF3 defects) to evade immune detection, inadvertently making them highly susceptible to oncolytic HSV-1 [Xia et al., 2016]. Therapeutic agents, such as the FDA-approved Talimogene laherparepvec (T-VEC), exploit this vulnerability by selectively replicating within these cells, leading to direct lysis and the release of tumor-associated antigens [Andtbacka et al., 2015]. This process subsequently stimulates a systemic immune response against the cancer, effectively turning the tumor into an in situ vaccine. The specificity of this target is defined by the intersection of viral tropism and the loss of cellular homeostasis typical of advanced malignancies [Martuza et al., 1991].

Other names

HSV-1 susceptible tumor cellsIFN-deficient malignant cellsNectin-1 positive tumor cellsOncolytic HSV target cells

Selective viral entry via Nectin-1 or HVEM followed by preferential replication in cells with defective Type I Interferon signaling, leading to direct oncolysis and induction of systemic anti-tumor immunity [Andtbacka et al., 2015; Campadelli-Fiume et al., 2007].