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Using our innovative antibody know-how to enhance the power of nature

David Humphreys, Discovery Science
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David Humphreys, Discovery Science
13-Sep-2021
 
Together with researchers at the University of Southampton, UCB used its antibody expertise and innovative protein engineering to harness part of the human immune system known as the complement cascade to enhance the natural ability of therapeutic antibodies to attack blood cancer cells.

Recently published in Communications Biology (part of the Nature portfolio) the new technology builds on previous research from UCB and harnesses a natural feature found at the end of Immunoglobulin M (IgM), an antibody with naturally high levels of complement activation, called a ‘tailpiece’. The tailpiece critically contributes to the formation of IgM hexamers. Antibody hexamerisation is a critical feature for activation of the complement system to attack cancer cells. By making a subtle modification to the tailpiece it enabled the Immunoglobulin G (IgG) - which is preferred for the treatment of human diseases - to retain its desirable properties but also take on the hexameric properties of IgM when bound to the target cell. This approach combines the best features of both antibody types into a single molecule and may open the way for a potential new class of treatments.

The new method was shown to be effective in several different antibodies. This makes it potentially attractive as a ‘plug-and-play’ modification tool to improve the performance of existing antibodies or create ‘bio-betters’ from existing therapeutics. To read more, the full (open access) paper can be accessed here.

The research was the product of a UKRI government-UCB co-funded PhD studentship collaboration (BBSRC grant BB/N5039927/1) between blood cancer experts at the University of Southampton and antibody engineering experts at UCB.

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