Engineered Herpes simplex virus type 2 (HSV-2 (engineered))

Engineered Herpes simplex virus type 2 (HSV-2) variants, such as those with deletions in the ICP10 protein kinase domain (ΔPK), are developed to selectively infect and lyse tumor cells, especially those with activated Ras or PI3K pathways[2][3][4]. These viruses exploit genetic vulnerabilities in cancers for tumor-selective replication and induce cell death via multiple programmed pathways (apoptosis, autophagy, pyroptosis), and are further able to stimulate antitumor immunity by triggering immunogenic cell death and recruiting dendritic and T cells[2][3][4]. While effective at eradicating cancer cells and cancer stem cells in preclinical models, their efficacy in clinical trials can be limited by host antiviral immunity, incomplete dissemination, and failure to replicate in quiescent cells[2][3]. HSV-2 oncolytic constructs have been studied in melanoma and other solid tumors and evaluated alone or in combination with immune checkpoint inhibitors[3].

Other names

Engineered HSV-2Oncolytic HSV-2HSV-2 ΔPK (for ICP10 protein kinase-deleted mutant)FusOn-H2 (HSV-2 construct with fusogenic activity)

Selective replication in tumor cells with aberrant Ras pathways\nDirect tumor cell lysis via virus replication\nActivation of apoptosis, autophagy, and pyroptosis in tumor cells\nStimulation of antitumor immune response by immunogenic cell death (release of DAMPs such as ATP and HMGB1)