Tumor cells permissive to G47Δ HSV-1 infection and replication (G47Δ-permissive tumor cells)

Tumor cells permissive to G47Δ HSV-1 infection and replication represent the specific cellular environment required for the therapeutic efficacy of the third-generation oncolytic herpes simplex virus type 1, G47Δ (Teserpaturev) (Todo et al., Cancer Res, 2001). These cells are characterized by their ability to support viral replication despite the virus's triple mutations, which include deletions of the γ34.5 and ICP47 genes and the inactivation of the ICP6 gene (Miyaji et al., Int J Mol Sci, 2021). Permissivity is often driven by the loss of normal antiviral defenses, such as the PKR-mediated protein synthesis shutoff, or by high levels of cellular ribonucleotide reductase that compensate for the viral ICP6 deletion (Fukuhara et al., Cancer Sci, 2016). When G47Δ infects these cells, it causes direct lytic destruction and releases tumor-associated antigens into the microenvironment (Todo et al., Nat Med, 2022). Furthermore, the deletion of ICP47 prevents the virus from inhibiting the Transporter associated with Antigen Processing (TAP), thereby enhancing MHC class I presentation in the infected tumor cells and stimulating a systemic T-cell response (Todo et al., Cancer Res, 2001). This dual mechanism of direct oncolysis and immune activation makes these permissive tumor cells the primary target for G47Δ therapy, which has been approved in Japan for the treatment of recurrent glioblastoma (Todo et al., Nat Med, 2022). Safety is maintained because normal, non-permissive cells possess intact antiviral pathways that restrict the replication of the attenuated virus (Miyaji et al., Int J Mol Sci, 2021).

Other names

G47delta-susceptible tumor cellsTeserpaturev-sensitive cancer cellsTriple-mutated HSV-1 target cellsDelytact-permissive cells

Oncolytic viral therapy involving selective replication in tumor cells leading to direct cell lysis and the induction of a systemic anti-tumor immune response through enhanced MHC class I expression and release of tumor antigens.