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Analyzing the antibodies
A general method for quantifying antibody drugs in blood will spur drug development and help personalise therapy
Kuo, C.H. et al.: “Development of a general method for quantifying IgG-based therapeutic monoclonal antibodies in human plasma using protein G purification coupled with a two internal standard calibration strategy using LC-MS/MS,” Analytica Chimica Acta (2018)
You don’t just need the right drug to treat disease, you also need the right dose. Not enough drug and it won’t have much effect, but too much and the side effects could be disastrous.
Monitoring the levels of some drugs in the body is not always easy, and this is especially true of an increasingly useful category of drugs made of antibodies. But this is starting to change.
“We have developed a general method for quantifying a particular category of therapeutic antibodies in blood plasma,” says Ching-Hua Kuo of National Taiwan University. She leads a team of researchers who report their innovative technique in Analytica Chimica Acta.
One key motivation driving the research is to personalise antibody treatment more effectively to match the specific needs of different patients, rather than relying on a less sophisticated “one dose for all” approach.
Antibodies, come in five basic forms, differing in the type of protein chains they contain. A high proportion of those that have been approved as drugs are of the ‘IgG’ type, which is the category that Kuo and her colleagues have targeted in their work to date. Those used as drugs are ‘monoclonal antibodies’, so called because they have been produced from cloned cells that manufacture identical antibodies tailored for a precise treatment rather than the mixture of antibodies commonly found in natural immune responses.
The new procedure quantifies the level of specific monoclonal IgG antibodies in a patient’s plasma by first incubating a sample of the plasma with beads carrying a protein that the IgG antibodies will selectively bind to. The trapped IgG molecules can then be released from the beads by chemical treatment and broken into fragments for analysis. The components of the resulting mixture are then quantified using the established analytical techniques of liquid chromatography (LC) and mass spectrometry (MS). These work by separating different molecules based on their rate of flow through a column (the LC process), followed by detecting individual molecules by their differing masses (the MS process). The researchers also developed a sophisticated calibration strategy to provide accurate results.
“Our method brings advantages in cost-saving convenience and especially flexibility which the typically used Enzyme-Linked ImmunoSorbent Assay (ELISA) method could not provide,” explains Kuo. The researchers have demonstrated their technique’s potential by quantifying three antibody drugs used to treat cancers and other conditions: bevacizumab, nivolumab and pembrolizumab. The plasma for these tests was obtained from cancer patients undergoing treatment.
The applicability of the method to different antibody drugs is another key advantage. “There was no general method for quantifying monoclonal antibody levels in human plasma until now,” Kuo emphasizes. Developing, testing and using these potent drugs should now become much easier.
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