Researchers at the University of Southampton and biopharma company UCB have found a way to enhance the natural ability of therapeutic antibodies to attack blood cancer cells using part of the human immune system known as the complement cascade, opening the way for a potential new class of treatments.
Published in Communications Biology, the new technology harnesses a natural feature of Immunoglobulin M (IgM), an antibody with naturally high levels of complement activation, and builds this property into Immunoglobulin G (IgG) antibodies, which are preferred for the treatment of human diseases. This approach combines the best features of both antibody types into a single molecule.
The new method uses innovative but simple protein engineering incorporating a modified IgM ‘tailpiece’, and has been shown to be effective in several different antibodies. This makes it potentially attractive as a “plug-and-play” modification tool for the cancer research community allowing them to improve the performance of existing antibodies or create ‘bio-betters’ from existing therapeutics.
The research was the product of a UKRI government-UCB co-funded PhD studentship collaboration between blood cancer experts at the University of Southampton and antibody engineering experts at the biopharma company UCB. Prof Mark Cragg at the University of Southampton said, “Antibody engineering is a fascinating area and allows us to take advantage of the fantastic molecules that nature has evolved to combat infection and improve on them for our therapeutic purposes”.
Researchers at UCB, Dr Shirley Peters and Dr David Humphreys said “This is a great example of grant funding enabling collaborative research which combines the strengths of both academia and industry. We at UCB could not have so comprehensively studied this invention without the expertise and research community at Southampton. UCB contributed innovative antibody expertise, which founded the concept and will enable it to further develop in the future. We are very pleased to be able to share our joint science with the global community with this paper”.
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Subject of Research
On-target IgG hexamerisation driven by a C-terminal IgM tail-piece fusion variant confers augmented complement activation
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