Monoclonal antibodies reactive with mucin glycoproteins found in sera from breast cancer patients.
Monoclonal antibodies to mucin glycoproteins have previously been shown to detect elevated antigen levels in sera from breast cancer patients. To determine whether different mucin epitopes represent better targets for serum assays, we have produced and characterized 14 new monoclonal antibodies directed against the mucin glycoproteins detected by antibody W1. Many of the new antibodies differed from each other in their ability to bind to mucins from various sources. Cross-competition analyses of antibody binding indicated that while epitopes for some antibodies were distinct, most epitopes showed complex structural or steric relationships with those for other antibodies. Antibody M26 bound glycolipids from meconium and kidney, indicating that it recognized a carbohydrate epitope. Antibodies M15, M22, M23, and M27 bound to structurally or sterically related epitopes on deglycosylated milk-derived mucin, suggesting that they recognized core protein epitopes. Enzyme immunoassays were developed with the new antibodies and evaluated for their ability to discriminate between sera from breast cancer patients and from controls with benign breast disease. The best single test in terms of sensitivity and specificity used a combination of two antibodies, antibody M29 for antigen capture and antibody M38 for antigen detection. A second test using antibody M26 for antigen capture and antibody M38 for antigen detection detected elevated antigen levels in sera from some patients which were in the control range of the M29/M38 test. By combining results from these tests, significantly more cancer patients were detected than with the W1 and CA 15.3 tests.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001943:Breast Neoplasms / Q000032:analysis*; D002241:Carbohydrates / Q000032:analysis; D000939:Epitopes / Q000032:analysis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009077:Mucins / Q000032:analysis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D002241:Carbohydrates; D000939:Epitopes; D008562:Membrane Glycoproteins; D009077:Mucins; C016424:epiglycanin protein, mouse