Experimental Study on Treatment of Gastric Cancer with New Recombinant Oncolytic Vaccinia Virus Infection Combined with Immune Effective Cells and Immune Checkpoint Blocking

Abstract

ObjectiveTo explore the significance of the combined strategy of oncolytic virus infection, immune effector cell supplement, and immune checkpoint blocking in the treatment of gastric cancer. MethodsA tumor-bearing nude mouse model of gastric cancer was treated with recombinant oncolytic vaccinia virus carrying the CXCL9 gene of T lymphocyte chemokine and IL-7gene (VV-IL7-CXCL9) obtained in previous experiments. We established a triple-intervention group of recombinant oncolytic vaccinia virus intratumoral injection+cytotoxic T lymphocyte (CTL)+immune checkpoint blocker (PD-1 monoclonal antibody), a single-intervention group of three measures, a dual-intervention group, and a blank control group. After the intervention, tumor-growth curve method, tumor-inhibition rate method, and bioluminescence method were used to detect the tumor treatment effect. ELISA was used to detect CXCL9 and IL-7 molecule concentration in the serum and tissue homogenate of animals in each group. ResultsThe therapeutic results of animal models showed that the tumor growth in the triple-intervention group of recombinant oncolytic poxvirus+CTL+immune checkpoint blocker (PD-1 monoclonal antibody) was significantly slower than those in the other intervention and the blank control group. ConclusionThe combination of recombinant oncolytic poxvirus intratumoral injection+CTL+immune checkpoint blocker (PD-1 monoclonal antibody) exert a strong antitumor effect in intervention experiments on gastric-cancer animal models.

Keywords

• gastric cancer
• oncolytic poxvirus
• immune effector cells
• immune checkpoint blocking therapy