Abstract 1462: Novel oncolytic virus armed with interleukin-21 enhances immune oncotherapy

Abstract Oncolytic viruses have elucidated the broad anti-tumor properties through selectively destroying tumor cells, promoting tumor antigen release and inducing the activation of immune response. Vaccinia virus (VV) has been engineered for tumor selectivity by the deletion of two essential genes (DDvv), viral growth factor (VGF) and thymidine kinase (TK). However, it still has certain obstacles, such as spread of virus, tumor microenvironment barrier, immune cell infiltration and tumor infiltration lymphocytes (TILs) proliferation. In the present study, we engineered the novel oncolytic mV01 and hV01 viruses, recombinant DDvv viruses carrying human interleukin-21 (hIL-21) or mouse IL-21 (mIL-21), respectively. mV01 and hV01 exhibited potent inhibition of various tumor cells with IC50 < 0.5 MOI. When in combination with hNK cell, hV01 significantly enhanced the inhibition of cell proliferation in SK-HEP-1 cells and HepG2 cells as compared to mock virus. Animal studies showed that mV01 (i.t.) significantly reduced tumor burden in B16 C57/BL6 xenograph mice that were pre-treated with low dose cyclosporine A (i.p), compared to mock virus treatment. Simultaneously, mV01 regimens improved tumoral immune cell infiltration and TILs proliferation. Additionally, in HCT116 NCG xenograph mice, administration of hV01 (i.t.) exhibited significant inhibition of tumor growth (T/C < 40%) when in combination with hNK cells (i.v). Together, these data revealed that V01 is a promising candidate for tumor immunotherapy through viral oncolysis and anti-tumor immunity. Citation Format: Rong Zhang, Tingting Wang, Yun Qing, Shuaijun Sun, Meili Liu, Fang Hu, Jin Fu. Novel oncolytic virus armed with interleukin-21 enhances immune oncotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1462.