Abstract A219: Using poxvirus to improve immunotherapy for brain glioma

Abstract

Oncolytic viral immunotherapy is a novel approach to cancer treatment. Viruses can directly kill cancer cells, provide antigens to dendritic cells to stimulate a T-cell response, and make cancer cells express genes of immune-enhancing cytokines locally within the tumor microenvironment. We used two types of poxvirus, myxoma virus and vvDD vaccinia virus (double deletion of vaccinia growth factor and thymidine kinase), to deliver IL-15/IL-15Rα gene (a cytokine that boosts the immune system) into brain gliomas. We found that the numbers of NK cells and CD8+ T-cells in the tumor area greatly increased and viable cancer cells substantially decreased after the injection of vvDD-IL15/IL15Rα virus. Vaccination of GARC-1 (a neoantigen for mouse glioma) with CpG and Incomplete Freund’s Adjuvant twice before tumor implantation together with vvDD-IL15/IL15Rα virus, rapamycin and celecoxib treatment after tumor implantation eliminated the gliomas. In order to mimic the clinical situation of treatment beginning after establishment of the tumor, GARC-1 specific CD8+ T-cells were adoptively transferred into tumor-bearing mice; when combined with oncolytic poxvirus (either Myx-IL15/IL15Rα or vvDD-IL15/IL15Rα), rapamycin, and celecoxib, this treatment can also cure gliomas. We already confirmed that IL15/IL15Rα, adoptive transfer of GARC-1 specific T-cells and celecoxib are essential components in this combination treatment. Current studies are evaluating the mechanism and contributions of different components of the treatment. Citation Format: Bingtao Tang, Claire Schane, Joanna Shisler, Edward Roy. Using poxvirus to improve immunotherapy for brain glioma [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A219.