Weekly newsletter:
November 30 - December 6 2020
Level difficulty:
Antibodies produced through genetic engineering are even more effective
The use of antibodies to combat human illness dates from the 1980s. They are the key component of the immune response. At that time, blood taken from rabbits infected with the diptheria bacteria were used to treat patients, even though the discovery of how antibodies work came later.
How exactly do they work? They can recognize a foreign molecule called an antigen, allowing different immune processes to be set in motion in order to neutralize the infectious agent. An antibody is made up of 2 regions: the Fc domain and the Fab domain. The Fab domain contains a variable antigen-binding region. The Fc domain is maintained between different antibodies and allows the binding of receptors found on the surface of numerous immune cells. One of the largest families of antibodies is the IgG which bind with FcɣR receptors. These receptors consist of 2 principal types: the FcɣR activators and the FcɣR inhibitors which respectively activate or inhibit the response paths of those immune cells that possess these two types of receptors, notably the T cells CD8+ (LT CD8+).
Today we still use antiviral serotherapy, to fight Sars-CoV-2 for example: the blood of individuals who have recovered from the infection is removed and used in the treatment of patients ill with COVID-19.
However, in contrast with this patient-derived serum, studies have highlighted the interesting nature of antibodies produced by genetic engineering to increase antiviral activity. Not all patients respond to these treatments in an optimal way and it’s important to develop antibodies that are effective against different pathologies. The antibodies produced by genetic engineering are widely used in treatment against cancer and auto-immune diseases. Indeed, of the 10 most sold medicines of 2019, 7 were antibodies made by this process.
The modification of antibodies by genetic engineering depends on identifying the amino acids and sugars in the Fc domain in order to increase or reduce their interaction with the different FcɣR receptors. In the treatment of cancers, it has been shown that a better interaction with this receptor allows the cells presenting antigens (CPA, notably the dendritic cells) to mature more fully, and prompts a more substantial response in the LT CD8, which destroy cancerous cells.
In the area of study into antibodies that enable patients to fight the virus, the role of the FcɣR has been little studied. Indeed, the Fab domain has been the main focus of research, since its binding to the antigen enables it to block the entry of virus particles into cells. By modifying the Fc domain we may be able to enhance the process of the destruction of infected cells.
It’s therefore very important that research into genetic engineering continues.
Xiaojie Yu, Mark S Cragg Engineered antibodies to combat viral threats. Nature, November 18 2020.
