title: Specific humoral immune response to the Thomsen-Friedenreich tumor antigen (CD176) in mice after vaccination with the commensal bacterium Bacteroides ovatus D-6.
abstract: The tumor-specific Thomsen-Friedenreich antigen (TFα, 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 TFα 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-TFα IgM and IgG antibodies which also bound to human cancer cells carrying TFα. Our data suggest that B. ovatus D-6 presents a unique TFα-specific immunogenicity based on a combination of several inherent properties including: expression of the true TFα antigen, clustering and accessible presentation of TFα 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 TFα-specific anti-tumor vaccine.
authors: Glycotope GmbH, Robert-Rössle-Str. 10, 13125, Berlin-Buch, Germany. philippe.ulsemer@glycotope.com
authors: Philippe
authors: P
authors: Ulsemer
authors: Gemma
authors: G
authors: Henderson
authors: Kawe
authors: K
authors: Toutounian
authors: Anja
authors: A
authors: Löffler
authors: Jens
authors: J
authors: Schmidt
authors: Uwe
authors: U
authors: Karsten
authors: Michael
authors: M
authors: Blaut
authors: Steffen
authors: S
authors: Goletz
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D001439:Bacteroides / Q000378:metabolism*; D019496:Cancer Vaccines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry; D007263:Infusions, Parenteral; D051379:Mice; D008809:Mice, Inbred C3H; D013270:Stomach / Q000382:microbiology
chemical_list: D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C016467:Thomsen-Friedenreich antigen
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