Scientists at the University of Southampton including those at the Centre for Cancer Immunology have developed a new method to understand how antibodies move in solution, which will help in their fight against cancer.
Antibodies are naturally generated by the body in response to viruses and bacteria but can also be engineered in the laboratory to find and kill cancer cells. However, not all antibodies developed for this purpose are successful. To help understand why, the Southampton team took a multidisciplinary approach involving chemists, structural biologists, immunologists and computer experts from across the University to develop new methods to study antibodies at much greater depth.
Traditional methods such as X-ray crystallography can generate an incredibly sharp picture of an antibody where every atom’s position is determined. However, this technique does not work for all antibodies and represents only a single, static snapshot of the antibody. An alternative method called small angle X-ray scattering (SAXS) can see what the antibody looks like in solution, but provides only a very fuzzy image, lacking detail.
Published in the Biophysical Journal, the Southampton team, alongside antibody experts in Sweden, developed a method using computer simulations called molecular dynamics (MD) that bridges the gap between these two techniques.
The team was able to see the antibody in solution more clearly, giving them new insight into the movements the antibody makes that might help determine activity.
The team used the new method to investigate an antibody targeted to a key immune receptor, CD32b. This receptor is important for controlling the immune system’s ability to become activated to fight cancer. Through understanding the antibody structure in more detail, the team now plan to design better antibodies to help improve the effectiveness of certain cancer immunotherapy treatments.
Funding for the study was provided by Cancer Research UK, the Institute for Life Sciences and the Hilary Marsden Scholarship for the provision of a PhD studentship.
Professor Mark Cragg, from the Centre for Cancer Immunology, said: “With this new technique, we are able to much better understand how antibodies interact with their targets, hopefully allowing us to develop more effective antibody drugs in the future.”
Jon Essex, Professor of Computational Systems Chemistry at the University of Southampton and co-senior author on the paper along with Dr Ivo Tews, Lecturer in Structural Biology said: “This exciting approach allows detailed atomic-level structural information to be recovered from low resolution experimental data using computer simulations. It could have a significant impact in antibody design”
The new Centre for Cancer Immunology, which opened earlier this year, is the first in the UK to be dedicated to cancer immunology research. The Centre is focused on the development of three main areas of immunotherapy: engineering monoclonal antibodies that can target specific proteins on the surface of cancer cells; using antibodies that specifically block negative signals and boost positive signals to anti-cancer killer T cells to dramatically restore immunity to cancer; and developing vaccines to fight cancer and give lasting protection.