Abstract 6906: Engineered bacteria launch and control an oncolytic virus

Abstract The ability of bacteria and viruses to selectively replicate in tumors has led to synthetic engineering of new microbial therapies. In our system, Salmonella has been programmed to produce Senecavirus A (SVA)-RNA and launch an SVA infection in bacterially-infected cancer cells. Utilizing time-lapse microscopy, we visualize S. typhimurium invasions into cancer cells and their subsequent delivery of multiple picornaviral species. S.-typhimurium-viral-RNA launch in vitro identified a small-cell-lung cancer cell line, H446, as a promising candidate for S.-typhimurium-SVA launch. This viral RNA-carrying Salmonella strain confers complete tumor regression in vivo. Finally, we integrate into this strain a protease-dependent mechanism to confer SVA-infection spatial localization. This work, to the best of our knowledge, is the first instance of bacteria delivering full-length viral RNAs for therapeutic oncolytic purposes. Citation Format: Jonathan Pabon, Zakary Singer, Hsinyen Huang, Charles Rice, Tal Danino. Engineered bacteria launch and control an oncolytic virus [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 6906.