Oncolytic virus(OV)is increasingly being recognized as a novel vector in cancer immunotherapy.Increasing evidence suggests that OV has the ability to change the immune status of tumor microenvironment,so called transf...Oncolytic virus(OV)is increasingly being recognized as a novel vector in cancer immunotherapy.Increasing evidence suggests that OV has the ability to change the immune status of tumor microenvironment,so called transformation of‘cold’tumors into‘hot’tumors.The improved anti-tumor immunity can be induced by OV and further enhanced through the combination of various immunomodulators.The Neo-2/15 is a newly de novo synthesized cytokine that functions as both IL-2 and IL-15.However,it specifically lacks the binding site of IL-2 receptorαsubunit(CD25),therefore unable to induce the Treg proliferation.In present study,a recombinant vesicular stomatitis virus expressing the Neo-2/15(VSVM51R-Neo-2/15)was generated.Intratumoral delivery of VSVM51R-Neo-2/15 efficiently inhibited tumor growth in mice without causing the IL-2-related toxicity previously observed in clinic.Moreover,treatment with VSVM51R-Neo-2/15 increased the number of activated CD8t T cells but not Treg cells in tumors.More tumor-bearing mice were survival with VSVM51R-Neo-2/15 treatment,and the surviving mice displayed enhanced protection against tumor cell rechallenge due to the induced anti-tumor immunity.In addition,combination therapy of OV and anti-PD-L1 immune checkpoint inhibitors further enhanced the anti-tumor immune response.These findings suggest that our novel VSVM51R-Neo-2/15 can effectively inhibit the tumor growth and enhance the sensitivity to immune checkpoint inhibitors,providing promising attempts for further clinical trials.展开更多
文摘Oncolytic virus(OV)is increasingly being recognized as a novel vector in cancer immunotherapy.Increasing evidence suggests that OV has the ability to change the immune status of tumor microenvironment,so called transformation of‘cold’tumors into‘hot’tumors.The improved anti-tumor immunity can be induced by OV and further enhanced through the combination of various immunomodulators.The Neo-2/15 is a newly de novo synthesized cytokine that functions as both IL-2 and IL-15.However,it specifically lacks the binding site of IL-2 receptorαsubunit(CD25),therefore unable to induce the Treg proliferation.In present study,a recombinant vesicular stomatitis virus expressing the Neo-2/15(VSVM51R-Neo-2/15)was generated.Intratumoral delivery of VSVM51R-Neo-2/15 efficiently inhibited tumor growth in mice without causing the IL-2-related toxicity previously observed in clinic.Moreover,treatment with VSVM51R-Neo-2/15 increased the number of activated CD8t T cells but not Treg cells in tumors.More tumor-bearing mice were survival with VSVM51R-Neo-2/15 treatment,and the surviving mice displayed enhanced protection against tumor cell rechallenge due to the induced anti-tumor immunity.In addition,combination therapy of OV and anti-PD-L1 immune checkpoint inhibitors further enhanced the anti-tumor immune response.These findings suggest that our novel VSVM51R-Neo-2/15 can effectively inhibit the tumor growth and enhance the sensitivity to immune checkpoint inhibitors,providing promising attempts for further clinical trials.
