Induction of alpha-N-acetylgalactosamine-O-serine/threonine (Tn) antigen-mediated cellular immune response for active immunotherapy in mice.
A block in carbohydrate chain elongation of O-glycosylated mucins results in accumulation of alpha-GalNAc O linked to serine or threonine (Tn antigen) in a large percentage of human adenocarcinomas. Immunization of mice with desialylated ovine submaxillary mucin (A-OSM), which contains a large concentration of Tn antigen, provided protection against challenge of a highly invasive Tn expressing syngeneic mouse mammary tumor, TA3-Ha. A similar protective effect was not observed in mice immunized with the deglycosylated mucin or irradiated TA3-Ha cells. Immunization with A-OSM but not with deglycosylated mucin resulted in high anti-Tn antibody response in mice. A-OSM induced in vitro proliferation of T-lymphocytes obtained from mice preimmunized with A-OSM or irradiated TA3-Ha cells. This antigen-specific T-cell response was significantly lower if lymphocytes were stimulated with either the deglycosylated or sialylated form of mucin. A-OSM stimulation induced primarily a CD4+ T-cell population, and these cells secreted interleukin 2 in a dose-dependent fashion. A-OSM was also able to induce delayed-type hypersensitivity in mice in response to footpad injections with irradiated TA3-Ha cells. These studies indicate that Tn antigen presented on a protein backbone is capable of providing cellular immunity and protection against tumor in mice.
Singhal
A
A
Biomembrane Institute, Seattle, Washington 98119.
Fohn
M
M
Hakomori
S
S
D000818:Animals; D000906:Antibodies / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology*; D015295:Antigens, Tumor-Associated, Carbohydrate; D004187:Disaccharides / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed; D007114:Immunization; D007167:Immunotherapy; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D009077:Mucins / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology
D000906:Antibodies; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D004187:Disaccharides; D007376:Interleukin-2; D009077:Mucins; C040286:Tn antigen; C016467:Thomsen-Friedenreich antigen