FB-631 as a promising therapeutic tool for the treatment of non-small cell lung carcinoma 2469

Description Aim Many NSCLC patients do not respond to current treatment options, or develop resistance in time. Therefore, developing therapeutic alternatives is an important focus of lung cancer research. Activation of the innate immunity response through stimulation of TLR7/8 is a promising strategy, but current TLR7/8 agonists are not safe for local administration in the lung. FB-631, a nanoparticle developed by Dr. Denis Leclerc, is a new TLR7 agonist, a potent activator of innate immunity, and was proven to be safe for administration via parenteral routes. Objective: Evaluate the impact of FB-631 on tumour development in a model of lung carcinoma. Methodology: Mice received FB-631 before or after the IV administration of CMT167 lung carcinoma cells. Cancer severity was reported upon sacrifice via the evaluation of lung index, and of a cancer score representative of the number and size of tumors. The pulmonary immune profile was also evaluated by flow cytometry. Results Cancer severity was significantly reduced in mice pre-treated with FB-631. This came with an increase in CD8 T cell and NK cell proportions in relation to tumor burden, and a modulation of regulatory molecules PD-L1/2 expression in vivo. In vitro, the stimulation of anticancer cDC1s with FB-631 increased IL-12 production and PD-L1/2 expression. Conclusion FB-631 can prevent the implantation of tumor cells and the development of tumors by supporting anti-tumor immunity, making it a promising tool for NSCLC treatment.