Tumor cells permissive to HSV-1 oncolytic replication

Tumor cells permissive to HSV-1 oncolytic replication refers to a specific physiological state of malignant cells that allows for the selective entry, replication, and cytolytic destruction by engineered Herpes Simplex Virus type 1 (HSV-1) [1]. While healthy cells typically mount a robust antiviral response through the Protein Kinase R (PKR) and Type I Interferon (IFN) pathways to block viral protein synthesis, many cancer cells harbor defects in these pathways to facilitate their own rapid growth and evasion of apoptosis [2]. This loss of innate immunity renders the tumor cells permissive, enabling oncolytic viruses like Talimogene laherparepvec (T-VEC) to replicate selectively within the tumor microenvironment [3]. Upon infection, the virus induces direct cell lysis (oncolysis), which releases tumor-derived antigens and damage-associated molecular patterns (DAMPs) [2]. This process transforms the immunosuppressive tumor microenvironment into an immunologically hot one, triggering a systemic T-cell mediated immune response against both the injected and distant metastatic lesions [1,4]. The selectivity of this approach is further enhanced by viral engineering, such as the deletion of the ICP34.5 gene, which ensures the virus cannot overcome the antiviral defenses of normal, non-permissive cells [3]. Citations: [1] Andtbacka RH, et al. J Clin Oncol. 2015;33(25):2780-8. [2] Kaufman HL, et al. Nat Rev Drug Discov. 2015;14(9):642-62. [3] Campadelli-Fiume G, et al. Rev Med Virol. 2011;21(4):213-26. [4] FDA. Imlygic (talimogene laherparepvec) Prescribing Information.

Other names

HSV-1 permissive cancer cellsOncolytic HSV-1 target cellsoHSV-susceptible tumor cellsPermissive malignant cells

Selective viral replication in tumor cells with defective antiviral pathways (e.g., PKR, IFN), resulting in direct oncolysis and induction of systemic anti-tumor immunity [1,2].