Anti-Tn human monoclonal antibodies generated following active immunization with partially desialylated ovine submaxillary mucin.
Partially desialylated ovine submaxillary mucin plus an immunological adjuvant has been used by us to induce a humoral immune response to Tn antigen and sialylated Tn in colon cancer patients at risk of recurrence. Peripheral blood lymphocytes were purified from one of these patients with a high IgM titer reactive with Tn antigen transformed with Epstein-Barr virus and subsequently fused with a human-mouse heteromyeloma cell line, HMMA2.11TG/O. Clones were screened and subcloned using an enzyme-linked immunoassay and four stable IgM-secreting clones were tested for reactivity with a variety of natural and synthetic antigens, paraffin-embedded colon carcinomas and normal colonic mucosa to determine their specificity. Four human IgM monoclonal antibodies reactive predominantly with Tn antigen were produced and shown to react with a mucinous human colon carcinoma cell line, LS-174T, and with paraffin-embedded human colon carcinomas. We conclude that modified ovine submaxillary mucin is an effective vaccine for generating a humoral immune response directed to Tn antigen present on human colon cancer.
O'Boyle
K P
KP
Montefiore Medical Center/Albert Einstein Cancer Center, Bronx, New York 10467.
Wright
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D000912:Antibodies, Neoplasm / Q000096:biosynthesis*; D000918:Antibody Specificity; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis; D007150:Immunohistochemistry; D051379:Mice; D009077:Mucins / Q000737:chemistry / Q000276:immunology*; D012756:Sheep; D012794:Sialic Acids / Q000737:chemistry / Q000276:immunology; D013363:Submandibular Gland / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology; D014611:Vaccination
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D000939:Epitopes; D007075:Immunoglobulin M; D009077:Mucins; D012794:Sialic Acids; C040286:Tn antigen