Antitumor effects of IL-12 and GM-CSF co-expressed in an engineered oncolytic HSV-1

Oncolytic viruses selectively replicate and destroy cancer cells while sparing normal cells, prompting their recognition as promising antitumor agents. Herpes simplex virus (HSV) is suitable as an anticancer agent, given its considerable therapeutic gene capacity and excellent safety profile in clinical trials. Interleukin (IL)-12 induces a Th1-type immune response that mediates interferon (IFN)-gamma release from natural killer (NK), CD4(+) and CD8(+) T cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the generation of antigen-presenting cells and promotes dendritic cell differentiation. We established a novel oncolytic HSV-1 ( increment 6/GM/IL12) co-expressing IL-12 and GM-CSF and tested its effects against a B16-F10 murine melanoma model. increment 6/GM/IL12 administration diminished tumor growth and prolonged survival compared to treatment with increment 6/GM or increment 6/IL12 expressing each individual cytokine. Flow cytometry and histological analysis showed increased activation of CD4(+) and CD8(+) T cells in increment 6/GM/IL12-treated mice. Enzyme-linked immunosorbent spot assay showed an increase in the phenotypically characterized IFN-gamma-producing cell population in increment 6/GM/IL12-treated mice. Moreover, increment 6/GM/IL12 induced a B16-F10-specific cytotoxic immune response that enhanced IFN-gamma production by CD3(+)CD8(+) T cells. Therefore, IL-12 and GM-CSF from an engineered oncolytic HSV have a synergistic effect, boosting the immune response to increase their antitumor effects.

Automated summary

This study demonstrated the synergistic effect of IL-12 and GM-CSF from an engineered oncolytic HSV, enhancing the immune response and improving the antitumor effects, particularly in inhibiting tumor growth and prolonging survival in a murine melanoma model. Increased activation of CD4(+) and CD8(+) T cells, along with enhanced IFN-gamma production and cytotoxic immune response, were observed in mice treated with increment 6/GM/IL12 compared to those treated with increment 6/GM or increment 6/IL12 expressing each individual cytokine.