Updated: Mar 13
Affinity maturation is a crucial process in the development of therapeutic antibodies, which are used to treat a wide range of diseases. One promising approach for achieving this is through the use of mammalian display technology, which enables the optimization of antibody binding and the development of more potent therapies.
In mammalian display, the antibody genes are fused to the genes that encode a cell surface protein, allowing for the display of the antibody on the surface of mammalian cells. This allows for easy screening of the antibodies for improved binding affinity and potency.
To carry out mammalian display, a library of antibodies is first generated, typically through the isolation of antibodies from an animal or human that has been exposed to the target antigen or through recombinant DNA technology. The library is then introduced into mammalian cells using various techniques, such as electroporation or viral transduction, and screened for the display of the antibody on the cell surface using methods like flow cytometry or fluorescence microscopy.
After screening, cells with the highest binding affinity for the target antigen can be isolated, and their antibody genes can be sequenced. This information can then be used to identify specific amino acid changes responsible for improved binding affinity, which can be incorporated into the original antibody to create a more potent therapeutic agent.
Protein engineering plays a critical role in optimizing antibody binding affinity. Rational design and directed evolution approaches can create libraries of variants with diverse amino acid sequences, which can be screened for improved binding affinity. Techniques such as site-directed mutagenesis or random mutagenesis can be carried out using various display technologies, including mammalian display.
One significant advantage of mammalian display technology is its ability to display antibodies in a more native-like environment, which mimics the natural binding of antibodies to cell surface proteins. This can lead to the identification of antibodies with improved specificity and affinity, reducing the risk of adverse immune reactions in patients.
Moreover, mammalian display technology can generate bispecific antibodies that bind simultaneously to two different targets. Bispecific antibodies can be useful in cancer immunotherapy, where they can target cancer cells while activating immune cells to attack the tumor.
In conclusion, mammalian display technology and protein engineering are powerful tools in optimizing the binding affinity of therapeutic antibodies. By displaying antibodies on the surface of mammalian cells and using rational design or directed evolution approaches, researchers can create more potent therapies with fewer side effects. With further research and development, these technologies hold immense potential to transform the field of biologic drug development, improving the lives of countless people worldwide.