Specific humoral immune response to the Thomsen-Friedenreich tumor antigen (CD176) in mice after vaccination with the commensal bacterium Bacteroides ovatus D-6

The tumor-specific Thomsen-Friedenreich antigen (TF alpha, CD176) is an attractive target for a cancer vaccine, especially as TF-directed antibodies play an important role in cancer immunosurveillance. However, synthetic TF vaccines have not overcome the low intrinsic immunogenicity of TF. Since natural TF-directed antibodies present in human sera are generated in response to microbes found in the gastrointestinal tract, microbial TF structures are obviously more immunogenic than synthetic TF. We recently isolated a new strain (D-6) of the human gut bacterium Bacteroides ovatus, which carries the true TF alpha antigen. Here, we present experimental data on the immunogenicity of this strain. Mice immunized with B. ovatus D-6 in the absence of adjuvants developed specific anti-TF alpha IgM and IgG antibodies which also bound to human cancer cells carrying TF alpha. Our data suggest that B. ovatus D-6 presents a unique TF alpha-specific immunogenicity based on a combination of several inherent properties including: expression of the true TF alpha antigen, clustering and accessible presentation of TF alpha as repetitive side chains on a capsular polysaccharide, and intrinsic adjuvant properties. Therefore, B. ovatus strain D-6 is an almost perfect candidate for the development of the first adjuvant-free TF alpha-specific anti-tumor vaccine.