Researchers at the University of Southampton, have gained unprecedented new insight into the key properties of an antibody needed to fight off cancer. Researcher revealed how changing the flexibility of the antibody could stimulate a stronger immune response.

Figure 1. The key properties of an antibody needed to fight off cancer.

Figure 1 shows that, the team investigated antibody drugs targeting the receptor CD40 for cancer treatment. Clinical development has been hampered by a lack of understanding of how to stimulate the receptors to the right level. The problem being that if antibodies are too active, they can become toxic.

Previous Southampton research has shown that a specific type of antibody called IgG2 is uniquely suited as a template for pharmaceutical intervention, since it is more active than other antibody types.

This latest research harnesses this property of the hinge and explains how it works: the researchers call this process 'disulfide-switching'. [1]

the Southampton team analyzed the effect of modifying the hinge and used a combination of biological activity assays, structural biology, and computational chemistry to study how disulfide switching alters antibody structure and activity. [2]

Dr Ivo Tews, Associate Professor in Structural Biology at the University of Southampton, said: “Our approach was to analyse the structure of the antibody in atomic detail, using the method of X-ray crystallography. While the resulting picture is very accurate, the information on how they move their ‘arms’ is missing, and we needed an image of the antibody in solution, for which we used an X-ray scattering approach called SAXS. We then used mathematical models and a chemical-computing approach to analyse the data, using the Southampton High Performance Computing cluster IRIDIS.”

Professor Mark Cragg, of the Centre for Cancer Immunology at the University of Southampton, said: “This study has given us new information about how to engineer antibodies to deliver a better immune response. We propose that more rigid antibodies enable the receptors to be bound closer together on the cell surface, promoting receptor clustering and stronger signalling for activity. This means by modifying the hinge we can now generate more or less active antibodies in a more predictable way.”

“Excitingly, our findings could have wider implications as it may provide a highly controlled and tractable means of developing antibodies for clinical use in future immunostimulatory antibody drugs.” [3]

References:

1. https://www.sciencedaily.com/releases/2022/07/220708141537.htm
2. https://health.economictimes.indiatimes.com/news/diagnostics/researchers-analyse-structure-of-antibodies-that-could-hold-the-key-to-more-effective-cancer-treatments/92795559
3. 3.https://www.zee5.com/articles/researchers-analyze-structure-of-antibodies-that-could-hold-the-key-to-more-effective-cancer-treatments

Cite this article:

Sri Vasagi K (2022), New Key Properties of Anti-Body to Fight Off Cancer, AnaTechMaz, pp.141