Abstract
ABSTRACTTherapeutic monoclonal antibodies (MAbs) are an important class of drugs used to treat diseases ranging from autoimmune disorders to B cell lymphomas to other rare conditions thought to be untreatable in the past. Many advances have been made in the characterization of immunoglobulins as a result of pharmaceutical companies investing in technologies that allow them to better understand MAbs during the development phase. Mass spectrometry is one of the new advancements utilized extensively by pharma to analyze MAbs and is now beginning to be applied in the clinical laboratory setting. The rise in the use of therapeutic MAbs has opened up new challenges for the development of assays for monitoring this class of drugs. MAbs are larger and more complex than typical small-molecule therapeutic drugs routinely analyzed by mass spectrometry. In addition, they must be quantified in samples that contain endogenous immunoglobulins with nearly identical structures. In contrast to an enzyme-linked immunosorbent assay (ELISA) for quantifying MAbs, mass spectrometry-based assays do not rely on MAb-specific reagents such as recombinant antigens and/or anti-idiotypic antibodies, and time for development is usually shorter. Furthermore, using molecular mass as a measurement tool provides increased specificity since it is a first-order principle unique to each MAb. This enables rapid quantification of MAbs and multiplexing. This review describes how mass spectrometry can become an important tool for clinical chemists and especially immunologists, who are starting to develop assays for MAbs in the clinical laboratory and are considering mass spectrometry as a versatile platform for the task.
Highlights
Therapeutic monoclonal antibodies (MAbs) are an important class of drugs used to treat diseases ranging from autoimmune disorders to B cell lymphomas to other rare conditions thought to be untreatable in the past
Currently, there are a limited number of commercially available clinical assays for quantifying therapeutic MAbs
Considering the double-digit growth rate of therapeutic MAbs, there will likely be a need for more clinical assays to quantify them in the near future
Summary
Therapeutic monoclonal antibodies (MAbs) are an important class of drugs used to treat diseases ranging from autoimmune disorders to B cell lymphomas to other rare conditions thought to be untreatable in the past. MAbs are larger and more complex than typical small-molecule therapeutic drugs routinely analyzed by mass spectrometry. They must be quantified in samples that contain endogenous immunoglobulins with nearly identical structures. As more patients undergo MAb therapy, there is a perceived need for monitoring of MAb therapeutic efficacy and understanding loss of response when patients fail treatment This poses an opportunity for the clinical laboratory to develop a new niche of tests and improve patient care by personalizing therapeutic regimens with MAbs. Therapeutic MAbs are typically modeled after human immunoglobulins (Igs), homodimers with a molecular mass of approximately 150 kDa. Each Ig consists of two identical glycosylated heavy chains (50 to 70 kDa) and two identical light chains (22 to 24 kDa). Therapeutic MAbs currently on the market are predominately IgG1 kappa, with a few being IgG2, IgG4, or hybrids
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