Distinguishing therapeutic monoclonal antibodies from patient monoclonal proteins by electrospray time-of-flight mass spectrometry

Abstract

Monoclonal gammopathies are a group of disorders characterised by proliferation of clonal plasma cells. Monoclonal intact immunoglobulin (Ig), free light chain and heavy chain proteins are routinely detected using electrophoresis and are important for diagnosis, monitoring and patient management. With the introduction of therapeutic monoclonal antibodies (tmAb), which are humanised monoclonal Ig proteins, for treatment of multiple myeloma and other disorders, protein electrophoresis is subject to interference from these therapeutics. They present as additional bands in the electrophoresis, complicating the interpretation of this investigation. The tmAbs cannot be distinguished from endogenous monoclonal proteins by current methods, which may lead to mis-diagnosis, and therefore incorrect patient management. We have developed an electrospray time-of-flight mass spectrometry (TOF MS) method which is able to detect tmAbs in patient serum and differentiate these from endogenous patient clones using accurate mass assignment of Ig light chains. The unique light chain mass of the tmAb can be identified and distinguished from patient monoclonal light chains. TOF MS also offers the advantage of being more sensitive than protein electrophoresis, enabling a lower limit of detection to be achieved.