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Antibody engineering: beginnings to bispecifics and beyond

Published on May 30, 2019 Reviewed on September 16, 2024   35 min

Other Talks in the Series: The Immune System - Key Concepts and Questions

Other Talks in the Series: Periodic Reports: Advances in Clinical Interventions and Research Platforms

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Hello. I'm Ian Wilkinson, the Chief Scientific Officer at Absolute Antibody, a contract research organization offering antibody sequencing, production, and engineering services to companies and academics working in the field of antibodies. I am giving a talk entitled, Antibody Engineering: Beginnings to Bispecifics and Beyond. In doing so, I will take you through the story of how monoclonal antibodies were first discovered through to their use, now, as highly-tailored biological therapeutics engineered to perform in a superior way to naturally occurring antibodies.
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Some of the earliest work in the field that would go on to become immunology, was first performed by Lady Mary Wortley Montagu and her colleagues. She brought the concept of variolation from the Ottoman Empire back to her homeland of Britain, and started to use live smallpox liquid as a very crude means of vaccination. This concept was famously taken a step further forward in 1798 by Edward Jenner. He inoculated a small boy from a pustule of a milkmaid suffering from the mild disease, cowpox, and injected this into the boy who then contracted the disease. After recovering, the boy was then subjected to the same process, but this time with a much more serious disease, smallpox. This time the boy did not get ill as he had gained an immunity having first being subjected to the very similar cowpox disease. This was the start of a smallpox vaccination. What neither Edward Jenner or Lady Montague realized at the time, was that it was antibodies that were at the heart of the immune response. Paul Ehrlich is arguably the father of modern immunology and was the first person to propose a model for an antibody which broadly speaking represents what we know to be true today. That is, a branched molecule that binds to its target, also known as antigen, and is responsible for activation of the immune response, including the complement pathway. By 1959, Edelman and Porter were describing the molecular structure of antibodies for which they were jointly awarded the Nobel Prize. Then, by 1972, the first atomic-resolution crystal structure of an antibody fragment was published. Interestingly, all of these achievements came before it was possible to produce monoclonal antibodies.

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