Tu152 - Exploring the Potential of Mycobacteria-derived Components in Anti-cancer Lymphocyte Activation

Abstract Text: Natural Killer (NK) cell-based therapies are promising but require overcoming several challenges like their short lifespan and the difficulty to obtain large numbers of efficient anti-tumor cells. Recently, we have developed a novel strategy generating robust anti-tumor NK cells which proliferate over other peripheral blood mononuclear cells, after priming with Bacillus Calmette Guérin (BCG), followed by weekly stimulation with low doses of IL-12, IL-15, and IL-21 cytokines. These NK cells, which can expand up to 200-fold without the need of cell sorting, exhibit strong cytotoxicity against a wide variety of solid tumors. Notably, NK cell expansion was successful regardless of the mycobacteria's viability.

Preliminary data have shown that mycobacterial extracts can enhance NK cell activation and degranulation against bladder cancer cells. Here, we describe that BCG subcellular fractions, or their combinations, could be used to enhance proliferation and anti-tumor function of NK cells and other innate lymphocytes, such as γδ T cells, depending on the BCG sub-strain used. Using three-dimensional (3D) cultures and organoid models, we further studied infiltration and solid tumor elimination by BGC-activated NK cells. We also explored the possibility of providing a more accurate donor selection using this preclinical testing model.