Therapeutic vaccines based on genetically modified Salmonella: a novel strategy in cancer immunotherapy

In the course of evolution, bacteria from the genus Salmonella adapted to survive and multiply in a vertebrate host. Skillful use of bacterial interactions with the host immune system became the basis for the development of modified Salmonella‑based therapeutic vaccines. Bacterial genome can be modified to reduce toxicity and to develop or enhance therapeutic activity. Salmonella‑based therapeutic vaccines are an attractive and novel alternative for conventional cancer treatment (chemotherapy, radiotherapy, and passive immunotherapy). Live bacteria have the natural ability to sense external environment and penetrate the target tissue. Appropriate strains of Salmonella, infused into experimental animal tumor model, accumulate selectively in solid tumors and inhibit their growth. Moreover, the bacteria can reach tumor areas that are inaccessible for other, passively diffusing therapeutics, e.g., ischemic areas. Thus, bacteria can produce and locally release a natural or recombinant anticancer agent, which enhances their therapeutic effect. S. typhimurium VNP20009 strain is safe, which has been documented in clinical trials. However, the expected therapeutic benefit has not been observed, presumably due to insufficient tumor colonization by bacteria. To enhance colonization of solid tumors, VNP20009 bacteria have been equipped with the ability to express on the surface an antibody fragment specific for carcinoembryonic antigen present on human tumor cells. Additionally, to potentiate antitumor activity, the genetic material of VNP20009 has been engineered to overproduce an endogenous proapoptotic protein, which targets cancer and immune cells promoting tumor growth.