Technique Predicts Stability of Potential Monoclonal Antibody Therapies

By measuring a property known as “colloidal stability,” researchers may be able to predict whether a potential antibody-based treatment will work early on in the drug development process.

Monoclonal antibody therapies have emerged as an important part of the medical armamentarium, from infectious diseases to cancer. These laboratory-produced molecules are engineered to bolster or substitute for the body’s immune response.

However, the treatments tend to require intravenous administration to reach the bloodstream in sufficient quantity, meaning oral formulations aren’t an option.

Now, scientists have discovered a single molecular indicator which can predict how viscous an antibody therapeutic will likely be, allowing drug developers to weed out options which might not be workable when taken out of in vitro tests and formulated for administration.

Results were published in Science Advances.

The results could have a long-term benefit in quickly filtering out unworkable drug candidates, but there’s also a shorter-term application.

“Selection of well-behaved antibodies with molecular properties that enable streamlined manufacturing, scale-up, and subcutaneous delivery is key for rapid development, particularly during a pandemic response,” study lead author Jonathan Kingsbury said in a press release.

The study team ultimately measured the viscosity and opalescence of 59 monoclonal antibody solutions, among them 43 already-approved products.

The measurements were correlated to an array of 23 molecular descriptors, and diffusion interaction was the most valuable in predicting inconsistencies. By testing the way light scatters through monoclonal antibody-based formulations, investigators were able to see how the protein would unfold in a solution and how its stability would be impacted.

The diffusion interaction parameter is a dilute-solution measure of colloidal self-interaction.

“No other descriptor, individually or in combination, was found to be as effective,” study authors wrote.

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