Transgenic Drug Discovery
A breakthrough in transgenic mice opens the door to “Humabodies.” Theodora Harold, CEO, and Brian McGuinness, Vice President, Business Development, both from Crescendo Biologics, provide background on the research and what it means for drug discovery.
Stephanie Sutton | | Interview
What’s the story behind Crescendo Biologics?
Crescendo Biologics is a spinout created using IP originally generated at the Babraham Institute in Cambridge, UK, funded by the Biotechnology and Biological Sciences Research Council. Prior to the formation of Crescendo, a research group led by Marianne Bruggemann laid the foundations for highly successful transgenic mice capable of generating fully human antibodies.
Part of what makes mAb-based therapeutics so successful is their superb binding specificity, but constraints imposed by their shape and size mean there are important therapeutic targets and indications that regular mAbs cannot address. Regular mAbs comprise two paired peptide chains – a heavy and light chain (H and L respectively). However, camels and llamas naturally produce a stable class of antibodies that lack the light-chain. These heavy-chain antibodies (HcAbs) contain the smallest unit of an antibody known to recognize and bind to its therapeutic target – the so-called VHH domain. Although camel-derived VHH molecules are a step towards creating the next generation of therapeutics that could address the shortcomings of mAbs, they are not ideal: 1) VHH are not “human” in origin and as such, are likely to be immunogenic when injected into humans; and 2) due to their structural adaptation, VHH are limited in their diversity, reducing the likelihood of successful outcomes in drug discovery.
An important paper published by Marianne’s group in 2007 observed that mice engineered to lack the ability to create antibody L-chains were able to spontaneously, albeit very inefficiently, generate their own HcAbs.
From this concept, Crescendo was born.
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