The Changes Of The MMP-2 And MMP-9 In The Remnant Tumor Tissue After Immunotherapy To B16

Objective The purpose of this study is to investigate the synergistically therapeutic effects of soluble PD-1 in combination with 4-1BBL and the therapeutic effects of IFN-γon melanoma and observe the invasive changes of the remnant tumor tissue after stopping therapy. Methods C57Bl/6 mice were inoculated i.m. With invariably amount of B16 cells in the right hind thigh muscle to establish the experimental melanoma model. The eukaryotic expression plasmids of soluble PD-1 (sPD-1) and 4-1BBL and IFN-γwere injected directly into the muscle for gene therapy, Observing the MMP-2, MMP-9 changes of the remnant tumor tissue after stopping therapy. The phenomenon IFN-γaffects the expressions of the MMP-2 and MMP-9 in vitro were observed. The expressions of 4-1BBL,sPD-1and IFN-γgenes in tumor microenvironment were detected by RT-PCR. Results The combination treatment of 4-1BBL and sPD-1 produced strong inhibition on tumor growth. So did IFN-γ. We stopped the gene therapy until three weeks. We noticed down-regulation of the expression of the MMP-2 and MMP-9 and up-regulation of the expression of IFN-γ. But after a week, the results were reverse. Conclusion it were obvious that the synergistically therapeutic effects of soluble PD-1 in combination with 4-1BBL and the therapeutic effects of IFN-γon melanoma. the remnant tumor cells increases the invasion when we stop the therapy during gene therapy. Therefore, it suggests the prolongation of the time of gene therapy is important to secure the stable therapeutic effects.