EXTH-42. DUAL ROLES OF PKR ORCHESTRATE ONCOLYTIC HSV SENSITIVITY AND ANTIGEN-SPECIFIC T CELL EXPANSION

Abstract The host immune system has developed many mechanisms to defend against and clear virus infections, including PKR, cGAS-STING TLR-MyD88 signaling pathways. Compromised anti-viral in tumor cells allows for infection, replication lysis by oncolytic viruses. However, compromised antiviral mechanisms, together with the microenvironment (TME), limit sensitivity of cells. We generated a novel Herpes simplex virus, oHSV-shPKR which disables tumor-intrinsic PKR signaling. significantly increases oHSV infection both virus-resistant sensitive glioblastomas (GBMs). Infection GBMs induces G2/M cell cycle arrest inhibits growth. activation antigen presentation through type I interferon its immune-stimulatory function increase tumor-antigen specific CD8 T-cell expansion, cytotoxic T lymphocytes. Preclinical studies showed that intra-tumoral injection human GBM patient derived xenograft (PDX) growth immune-deficient NSG mice murine orthotopic immunocompetent mice. results demonstrate potential be used clinical applications oHSV-resistant treatment.