Mechanisms of anticancer activity of bacteria in enhancing cancer immunotherapy.

Abstract

e15047 Background: Numerous studies indicate that selective microbiota could enhance anti-tumor immunity with checkpoint inhibitors. However, it is arduous to identify the best candidate bacteria strains and understand their underlying action mechanisms. Methods: We have developed Avatiome platform technology, an innovative pre-clinical model system that mimics the human body's immune system and microbiome. Avatiome incorporates up-to-date technologies such as immunophenotyping, single-cell transcriptomics, and an Artificial Intelligence system to develop novel therapeutics targeting neuronal, systemic inflammatory diseases, and cancers. Results: We have identified Lp IMB19 as an LBP candidate that can enhance anti-cancer immunity through this technology. Lp IMB19 suppresses tumor progression in pre-clinical models of melanoma, renal cancer, and NSCLC. Lp IMB19 efficiently potentiates the therapeutic effect of anti-PD-L1 in murine tumor models by enhancing the effector function of CD8+ T cells via altering the phenotypes of tumor-infiltrating macrophages with inflammatory M1 type. We have identified rhamnose-rich heteropolysaccharides (RHP) as key effector molecules to induce M1 macrophage in a TLR2 dependent manner. Lp IMB19 also limits the amount of iron availability via Lipocalin 2 (LCN2) to capture trace iron from the microenvironment and switch to an iron sequestration phenotype, subsequently inhibiting tumor growth. No side effect or toxicity is observed in pre-clinical toxicity studies. Conclusions: We are currently developing Lp IMB19 as an onco-biotics for clinical investigation as a live biotherapeutic product (LBP) combined with immune checkpoint inhibitors.