After the advent of radiation therapy and chemotherapy, Bacteria-mediated cancer therapy introduced in the late 19th century by William B. Coley, with his Coley’s toxins Streptococcus pyogenes to treat inoperable sarcomas, gradually disappeared from medical practice. However, recent progress in the fields of immunology and biotechnology has revived the mechanism underlying the activity of Coley’s toxin, meaning that bacteria have returned to the agenda of those undertaking cancer researches. In the past 20 years, bacterial cancer therapy has again become a hot topic, and various kinds of bacteria have been the subject of preclinical and clinical research.
The specific hypothesis behind the project was 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. Therefore, BaCTher project has been conceived to investigate a novel strategy to expand the current arsenal of anti-tumor weapons in order to overcome the intrinsic limitations of standard anti-cancer therapies.
During the first year of the project we demonstrated that STMΔznuABC is able to reach the tumor zone and to specifically localize around tumor cells; we identified specific involvement of immune cells demonstrating that STMΔznuABC was able to recall more immune cells in the TME, in both primary and secondary metastatic tumor of treated mice compared to the untreated mice; and the ability of STMΔznuABC to induce the modification of the TME and the systemic immune system.
We demonstrated, during this second part, that STMΔznuABC has anti-tumor activity not only in syngeneic breast cancer mice model, as demonstrated during the first year of the project, but also on genetically engineered breast cancer-prone female mice and chemically fibrosarcoma cancer mouse model. STMΔznuABC, indeed, is able to reach the tumor zones, tumors of different embryological origin, significantly reduce the tumor growth and significantly increase the survival of the tumor-bearing mice compared to the untreated group.
