title: Human anti-mouse antibodies: pitfalls in tumor marker measurement and strategies for enhanced assay robustness; including results with Elecsys CEA.
abstract: Therapies using monoclonal antibodies may have undesirable consequences for the diagnostic use of tumor markers. These effects can be minimised by employing chimeric antibodies as well as special interference eliminating reagents. Human Anti-Mouse Antibodies (HAMA) are produced as a result of the immune response of a patient to treatment with murine monoclonal antibodies. The interaction of HAMA with the murine monoclonal antibodies of a tumor marker assay can simulate (false) positive or negative results leading to misdiagnosis and to inadequate disease management of a patient. To avoid HAMA-interferences "Roche Diagnostics" established a three-component-system: The use of chimeric antibodies, the interference elimination, which is realised in the parameters most frequently used like CEA and TSH. By employing such a chimeric antibody, Elecsys CEA proved to be extremely robust against HAMA-interferences. With 20 clinical relevant samples from different Mab-approaches, no HAMA-interference was observed. By fragmentation of the antibodies, i.e., elimination of the constant region and using monovalent fab-fragments (antigen binding fragment) combined with the addition of special blocking reagents all not-chimerized, Elecsys assays showed comparable results to chimerisation. This could also be shown with 20 clinical relevant samples.
authors.affiliation: Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Nussbaum
authors.forename: H J
authors.initials: HJ
authors.lastname: Roth
mesh_terms: D000818:Animals; D000906:Antibodies; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D018394:CA-125 Antigen / Q000032:analysis; D018395:CA-19-9 Antigen / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000032:analysis; D019937:Diagnostic Techniques and Procedures; D006801:Humans; D051379:Mice; D011786:Quality Control; D011933:Reagent Kits, Diagnostic; D011993:Recombinant Fusion Proteins
chemical_list: D000906:Antibodies; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018395:CA-19-9 Antigen; C083825:CA-72-4 antigen; D002272:Carcinoembryonic Antigen; D011933:Reagent Kits, Diagnostic; D011993:Recombinant Fusion Proteins