Human anti-mouse antibodies: Pitfalls in tumor marker measurement and strategies for enhanced assay robustness; including results with Elecsys (R) CEA

Therapies using monoclonal antibodies may have undesirable consequences for the diagnostic use of tumor markers. These effects can be minimised by emp loying chimeric antibodies as well as special interference eliminating reag ents. Human Anti-Mouse Antibodies (HAMA) are produced as a result of the im mune response of a patient to treatment with murine monoclonal antibodies. The interaction of HAMA with the murine monoclonal antibodies of a tumor ma rket assay can simulate (false) positive or negative results leading to mis diagnosis 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 realise d in the parameters most frequently used like CEA and TSH. By employing suc h a chimeric antibody, Elecsys(R) CEA proved to be extremely robust against HAMA-interferences. With 20 clinical relevant samples from different Mab-a pproaches, no HAMA-interference was observed. By fragmentation of the antib odies, i.e., elimination of the constant region and using monovalent fab-fr agments (antigen binding fragment) combined with the addition of special bl ocking reagents all not-chimerized Elecsys(R) assays showed comparable resu lts to chimerisation. This could also be shown with 20 clinical relevant sa mples.