Abstract 3525: Lactobacillus plantarum IMB19 enhances anti-tumor immune response by modulating multi-layered innate and adaptive immunity

Abstract Intestinal commensals are being increasingly appreciated for their role in modulating the therapeutic efficacy of cancer therapies. Human-associated bacterial strains with demonstrable modulation of anti-tumor immune responses have great potential to be developed as biotherapeutics.We developed the AVATIOME࣪ model, a screening prototype based on murine primary immune cells, rationally targeting the innate and adaptive immune system to identify immuno-stimulating commensals.Our lead Lactobacillus plantarum IMB19 (Lp IMB19), suppresses tumor progression in pre-clinical models of melanoma, renal cancer, and NSCLC. LpIMB19 efficiently potentiates the therapeutic effect of anti-PD-L1 in murine tumor models. A capsular component of LpIMB19, structurally defined as rhamnose-rich hetero-polysaccharide (RHP) recapitulates the anti-tumor efficacy of live bacteria.The TLR2 agonist specifically targets macrophages towards an inflammatory phenotype followed by an increase in the activity of CD8+ IFNy+ T-cells. LpIMB19 and RHP enhance iron sequestration by activated macrophages in the tumor microenvironment through a defined mechanism. Thus, depriving tumor cells of iron and suppressing tumor cell proliferation. Translational investigations revealed the efficacy of LpIMB19 in urinary bladder xenograft studies.LpIMB19 mediated iron sequestration by inflammatory tumor macrophages, a byproduct of innate immune activation along with systemic CD8+ T-cells activation leads to enhancement of anti-tumor immunity. Our data on human cancers suggests the applicability of LpIMB19 as a potential onco-microbiotic. Currently, LpIMB19 is being progressed for clinical investigation as a live bio-therapeutic product (LBP) in combination with immune check-point inhibitors. Citation Format: Garima Sharma, Amit Sharma, Inhae Kim, SooWoong Lee, Hae-Na Lee, ChangWook Park, Sin-Hyeog Im. Lactobacillus plantarum IMB19 enhances anti-tumor immune response by modulating multi-layered innate and adaptive immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3525.