CXCL11-Armed oncolytic poxvirus elicits potent antitumor immunity and shows enhanced therapeutic efficacy.

ABSTRACT: We have armed a tumor-selective oncolytic vaccinia virus (vvDD) with the chemokine (CK) CXCL11, in order to enhance its ability to attract CXCR3⁺ antitumor CTLs and possibly NK cells to the tumor microenvironment (TME) and improve its therapeutic efficacy. As expected, vvDD-CXCL11 attracted high numbers of tumor-specific T cells to the TME in a murine AB12 mesothelioma model. Intratumoral virus-directed CXCL11 expression enhanced local numbers of CD8⁺ CTLs and levels of granzyme B, while reducing expression of several suppressive molecules, TGF-β, COX2, and CCL22 in the TME. Unexpectedly, we observed that vvDD-CXCL11, but not parental vvDD, induced a systemic increase in tumor-specific IFNγ-producing CD8⁺ T cells in the spleen and other lymph organs, indica

SUBMITTER: Liu Z 

PROVIDER: S-EPMC4839379 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature