Abstract 6662: Modified oncolytic viruses with immunomodulatory genes enhance anti-tumor efficacy

Abstract

Abstract While chemotherapy and radiotherapy are considered first-line treatments for most cancers, their significant side effects have prompted ongoing innovation and the discovery of novel cancer treatment strategies. Oncolytic viruses (OV) as one of the most advanced cancer treatments have shown promising results in treating otherwise untreatable types of cancer in last two decades. After selectively targeting tumor cells, OVs could directly kill cancer cells, and induce a powerful anti-cancer immunity. Recently, we evaluated the anti-tumor effect of a modified OV (mOV) in vitro and in vivo. Firstly, the expression of the transgenes were validated on different tumor cells by FCM and ELISA assay. The results showed that a susceptible cell line was identified which has high expression efficiency of transgenes. In order to evaluate the cytotoxicity of mOV, CCK-8 assay was performed on 30+ tumor cell lines. It indicated that mOV has stronger killing effect on susceptible cells through inducing cellular apoptosis. To further evaluate the biological activity of the transgenes on immune cells, mOV-infected tumor cells and supernatant were collected to treat T cell, NK cell or MoDC. The results demonstrated that mOV infection could significantly promote T cell and NK cell activation, and increase the maturation of moDC cells, resulting in the secretion of IFN-γ by CD8+ T cells. In the in vivo efficacy study, MC38 syngeneic model was used to test the anti-tumor effect of mOV. The result showed that mOV could significantly inhibit the growth of the treatment side tumor, and reduce the contralateral tumor to a certain extent. Blood FCM analysis revealed that the percentage of IFN-γ+CD3+, IFN-γ+CD4+ and IFN-γ+CD8+ T cells were markedly increased by mOV treatment compared with vehicle. In addition, IHC analysis of tumor showed that mOV treatment could promote the infiltration of CD4+, CD8+ and CD86+ positive cells. To study the safety or PK of the mOV, viral bio-distribution and shedding assay were performed to detect viral genome at different tissues or excreta. It indicated that mOV was almost undetectable or at very low levels for 14 days after administration. In conclusion, our study revealed that modified OVs with immunomodulatory genes have good anti-tumor efficacy both in vitro and in vivo, which could obviously induce the activation of several immune cells. Moreover, the mOV genome was almost undetectable or at very low levels in mouse tissues and excreta. Keywords: Oncolytic virus, immunotherapy, immunomodulatory genes Citation Format: Zhongbao Song, Guangxu Ding, Anran Xia, Wanqing Ma, Qiuhong Li, Chenhui He, Xu Chen, Zhixiang Zhang, Qingyang Gu. Modified oncolytic viruses with immunomodulatory genes enhance anti-tumor efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6662.