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.

Tumor‐associated antigens: Tn antigen, sTn antigen, and T antigen

“…Recently, T antigen vaccination (commensal bacterium Bacteroides ovatus D‐6) has been reported in human acute myelogenous leukemia cell line KG‐1. This supports the argument that the Bacteroides ovatus D‐6 strain is an almost perfect candidate for the development of the first adjuvant‐free T antigen‐specific anti‐tumor vaccine .…”

Profiling of Naturally Occurring Antibodies to the Thomsen-Friedenreich Antigen in Health and Cancer: The Diversity and Clinical Potential

“…There is strong evidence that TF Abs may be induced by TF-positive enteric bacteria [25,[56][57][58]. The increase of the IgM TF Ab level after per os Bacteroides xylanisolvens and ovatus D-6 TF-positive strain application [56,84] supports the idea that the microbiome induces the generation of systemic Ag-specific Abs against sugar epitopes, including TF. An increased IgG response to TF has been found in H. pylori-infected individuals, but mostly in those with Lewis (a-) phenotype [85].…”

“…There is strong evidence that the risk of specific cancers is associated with alterations of human microbiome, pointing to a possible contribution of the immune response to commensal microbiota to the risk of some cancer types [99]. The microbiome inducing induction of antigen-specific antibodies against microbial sugar epitopes, including TF, was proposed as a possible way to modulate antitumor immunity through dietary supplementation of selected commensal bacteria [84].…”

The Prospects for the Therapeutic Implications of Genetically Engineered Probiotics

“…e combined benefits of GM probiotics, including their direct antagonistic response against pathogenic bacteria as well as the immunomodulatory potentials against [103] Intestinal inflammation Bacteroides ovatus V975 Mice Decreased the symptoms of DSS-induced colitis in a mice colitis model [103] Clearance of infectious agents…”