Nanosensors ‘could help guide antibody production’
pharmafile | August 20, 2013 | News story | Manufacturing and Production | Massachusetts Institute of Technology, Nanosensors, antibody production
Researchers in the US have developed a system based on nanosensors that could not only improve antibody-based medicines but also make them easier and cheaper to produce.
The team from Massachusetts Institute of Technology (MIT) used a briefcase-sized array of billions of nanoscale sensors to screen various different types of antibodies for their binding strength to a specific protein, according to the study in ACS Nano.
The nanosensor arrays could be used to monitor the structure of the antibodies, for example to check whether they carry a carbohydrate side chain that might interfere with their activity, and also to determine which cells provide the best yields of the antibody in culture.
The researchers point out that for antibodies to be effective they must bind strongly to their target. No less important, however, is the development of a robust manufacturing process that reduces the risk of producing batches of antibody that lack consistency and uniformity in binding.
Using the nanosensors, drug companies could make the current approach of testing batches for effectiveness much quicker and more efficient, but it also raises the prospect of fine-tuning the manufacturing process to generate a more consistent product.
“You could use the technology to reject batches, but ideally you’d want to use it in your upstream process development to better define culture conditions, so then you wouldn’t produce spurious lots”, commented lead author Nigel Reuel, a scientist in the lab of MIT professor of chemical engineering Michael Strano.
It can also be used to screen cell culture organisms to find the most productive cells, which can then be analysed to identify the genetic profiles that distinguish them from their less productive counterparts, and potentially to monitor antibody levels and quality online during production.
Glycosylation patterns
Meanwhile, the MIT team says another useful application of the nanosensors would be to measure weak binding interactions, which could also help with antibody drug manufacturing.
Antibodies are usually coated (glycosylated) with carbohydrate chains that are necessary for the drugs to be effective, but are hard to detect because they interact weakly with other molecules.
Cells used to manufacture antibodies are also engineered to add the side chains, but the process is difficult to control as it can be influenced by variables like temperature and pH.
“This has been a problem for pharmaceutical companies and researchers alike, trying to measure glycosylated proteins by recognising the carbohydrate chain”, according to Strano, who noted the tool could help researchers determine the optimal conditions for the correct degree of glycosylation to occur.
‘”What a nanosensor array can do is greatly expand the number of opportunities to detect rare binding events”, he added.
The work was funded by Novartis and the US National Science Foundation, and the pharma company is now testing a prototype of the nanosensor array.
Phil Taylor
