Development of Salmonella vaccines for cancer and viruses

National Institute Of Allergy And Infectious Diseases

Investigators

Abstract

Salmonella are one of several different bacteria that have been shown to colonize solid tumors and are considered a leading contender for the development of bacterial-mediated anti-tumor therapy. Live recombinant attenuated Salmonella can be used to deliver proteins, DNA plasmids or other molecules directly to solid tumors or the tumor microenvironment. Salmonella can be delivered orally, are inexpensive to produce and can elicit both mucosal and systemic immune responses. Our goal is to engineer a safe attenuated strain to target solid tumors either alone or in combination with other treatments such as chemotherapy or immunotherapy. For the initial screening and identification of Tumor Colonization Factors of Salmonella Typhimurium and strain development, we are using a well-characterized melanoma model in which B16 melanoma cells are inoculated in the syngeneic C57BL6J mouse strain. Since C57BL6J mice are highly susceptible to infection with Salmonella Typhimurium, due in part to the lack of functional Nramp1/SLC11A1, we will also use Nramp1 reconstituted mice. Attenuated Salmonella Typhimurium strains will also be adapted to deliver chemotherapy or anti-tumor molecules (e.g. nanobodies) directly to tumors. Once promising Salmonella strains have been identified we will test additional in vivo models for metastasis in mice, including a model where human tumors can be xenografted into mice (in collaboration with Alana Welm).