ISTITUTO SUPERIORE DI SANITA

Cancer is the second cause of death in the western world and it is expected to become the leading one in developing countries in the next future. The long-term outcome of BaCTher is the improvement of the cancer treatment that can overcome the intrinsic limitations of the current therapies through the development of a new promising therapeutic strategy. The specific hypothesis behind the proposed research is that an attenuated Salmonella enterica serovar Typhimurium (STMΔznuABC) is able to influence the tumor microenvironment (TME) reprogramming or re-educating the immune response, and inducing a shift from protumorigenic inflammation to anticancer immunity, which results in a tumor growth control. This hypothesis is based on the observation that: 1) there is compelling scientific evidence of the effect of bacteria, and in particular Salmonella, against cancer growth; 2) STMΔznuABC is able to reduce cancer growth and to increase the average life expectancy in a mammary adenocarcinoma Balb/c mice model; 3) STMΔznuABC is able to penetrate and proliferate into the tumor cells inhibiting the proliferation of tumor cells at 24h post-treatment. Three specific aims are designed to: 1) investigate the relationship between STMΔznuABC and TME; 2) characterize the mechanism of STMΔznuABC antitumor activity; 3) validate the results obtained in the preliminary studies using alternative in vivo models. The Experienced Researcher (ER), from the Istituto Superiore di Sanità (ISS), Italy, will spend one year at the Cancer Immunobiology Section of the Cancer and Inflammation Program (CIP), Center for Cancer Research (CCR), division of the National Cancer Institute (NCI), Bethesda, MD USA, for mutual exchange of skills and know-how that will be transferred back to the beneficiary organisation (ISS), contributing to the establishment of a wider long-term collaboration between the ER and host institutions.