Abstract

Abstract The microbiome's diverse functions in human health have generated increasing interest in using live bacteria for cancer therapy. Due to their natural presence in colon, lung and breast tissue, bacterial therapies have been augmented using synthetic biology in order to treat infections, inflammation, and cancer. One major challenge is finding safe and effective host species and therapeutic payloads for a particular type of cancer. Here we explored the vast diversity of microbial isolates in the environment as a valuable source of novel therapeutic compounds that can be expressed by bacteria. Specifically, we isolated and identified soil bacteria from 25 local parks, and investigated their secreted compounds for anti-cancer activity using monolayer and 3D-spheroid cultures of lung cancer. Through metagenomic analysis, toxicology assays, varied growth conditions, and bacteria-cancer co-culture experiments, we found Bacillus spp. isolates from Manhattan parks' soil that secreted products with high, dose-dependent cytotoxicity against lung cancer models. We also demonstrate that Bacillus subtilis, a model organism for gram-positive bacteria, can colonize lung cancer tumor spheroids, pointing to its use as a viable strain for bacteria cancer therapy. The work presented here underscores the potential of harnessing environmental microbial diversity for the development of gram positive species and their compounds as cancer therapeutics. Citation Format: Dhruba Deb, Tal Danino. Bacterial lung cancer therapeutics from soil bacteria in New York City [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 2186.

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