A novel cocktail therapy based on quintuplet combination of oncolytic herpes simplex virus-2 vectors armed with interleukin-12, interleukin-15, GM-CSF, PD1v, and IL-7 × CCL19 results in enhanced antitumor efficacy

Virol J. 2022 Apr 22;19(1):74. doi: 10.1186/s12985-022-01795-1.

Abstract

Background: Selectively replicating herpes simplex virus-2 (HSV-2) vector is a promising treatment for cancer therapy. The insertion of multiple transgenes into the viral genome has been performed to improve its oncolytic activity.

Methods: Herein, we simultaneously constructed five "armed" oncolytic viruses (OVs), designated oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19. These OVs delete the ICP34.5 and ICP47 genes with the insertion of transgenes into the deleted ICP34.5 locus. The anti-tumor efficacy in vivo was tested in the syngeneic 4T1 and CT26 tumor-bearing mice model.

Results: The OVs showed comparable oncolytic capability in vitro. The combination therapy of oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19 exhibited the highest tumor inhibition efficacy compared with the treatment of single OV or two OVs combination.

Conclusions: The OVs armed with different transgenes combination therapy also named 5-valent oHSV2 (also called cocktail therapy) might be an effective therapeutic strategy for solid tumors.

Keywords: 4T1; CT26; Combined therapy; Oncolytic herpes simplex virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Genetic Vectors / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Herpesvirus 2, Human / genetics
  • Interleukin-12 / genetics
  • Interleukin-15 / genetics
  • Interleukin-7 / genetics
  • Mice
  • Neoplasms* / drug therapy
  • Oncolytic Virotherapy* / methods
  • Oncolytic Viruses* / genetics

Substances

  • Interleukin-15
  • Interleukin-7
  • Interleukin-12
  • Granulocyte-Macrophage Colony-Stimulating Factor