Development of Salmonella-based cancer vaccines

Abstract

One of the major limitations of the modern cancer vaccines is poor delivery of tumor-associated antigens (TAAs) to the intact professional antigen- presenting cells (APCs). To address this challenge, attenuated viral or bacterial vectors have been used in experimental cancer vaccines to deliver TAAs to the host APCs in situ. From the clinical application prospective, Salmonella -based vectors have an advantage because of excellent safety record of an FDA-approved oral vaccine for typhoid fever and potent immunogenicity with low toxicity in humans shown by recently developed attenuated strains. Live attenuated Salmonella vectors have been used in experimental cancer vaccines to deliver TAAs in the form of either DNA or protein. Of particular promise are Salmonella -based recombinant vaccines in which a TAA of choice is expressed and delivered to the cytosol of professional APC using effector proteins of the Salmonella Pathogenicity Island 2-encoded type III secretion system. This chapter reviews strategies of using natural properties of Salmonella for construction of effective cancer vaccines and their clinical translation.