Enhanced Oncolytic Immunotherapy: Advancing HSV-1 as a Therapeutic Agent

This study focused on enhancing the therapeutic potential of HSV-1 as an oncolytic immunotherapy agent. The research aimed to improve the virus's ability to selectively target and destroy tumor cells while stimulating the immune system. A selection process identified a potent strain of HSV-1 from clinical samples, which was then genetically modified to increase its oncolytic and immunogenic properties. The modified virus incorporated a gene for a highly fusogenic glycoprotein to enhance tumor cell killing and the release of immune-activating factors. Additional armed derivatives were created to boost the immune response at the site of tumor destruction, expressing various immune-stimulating proteins.

The in vitro and in vivo experiments demonstrated that the modified HSV-1 strain effectively killed tumor cells and induced a robust immune response. The expression of the fusogenic glycoprotein resulted in increased release of immune-activating molecules and enhanced cell surface expression of a protein associated with immunogenic cell death. In animal models, the virus showed promise in treating both injected and distant tumors, with evidence of immune memory and increased CD8+ T cell levels.

The study concluded that the HSV-1 platform offers a versatile approach to developing new oncolytic immunotherapies. The modifications made to the virus are expected to be most effective when used in combination with other cancer treatments, particularly PD1/L1-targeted therapies. The lead virus from this research, which expresses the fusogenic glycoprotein and a human granulocyte-macrophage colony-stimulating factor, has advanced to clinical development and is being evaluated alone and in combination with anti-PD1 therapy across various tumor types.