Several recent publications from the rockstar team at GigaGen illustrate how they are using the BioXp® system to streamline antibody drug discovery workflows. It’s tough to overstate the importance of this area of research: monoclonal antibodies, antibody drug conjugates, and single-domain antibody variants have become invaluable for their robust recognition and downstream regulation of human immunologic processes. Using antibodies to recognize cancer-related antigens and stimulate an immune attack, for example, is essential for many cancer treatments, while neutralizing antibodies for autoimmune and inflammatory diseases bind to and prevent pro-inflammatory factors from exacerbating the immune response.
At GigaGen, scientists have made remarkable progress in antibody drug discovery. Along the way, they have carefully honed the methods — or even come up with new techniques — to improve the results of these workflows.
In a recent publication in the journal mAbs, lead author Jan Fredrik Simons, senior author David Johnson, and collaborators evaluated two different mutagenesis methods to determine how they contribute to in vitro affinity maturation. They used our BioXp® system to generate full-length constructs, and to introduce them into a vector for expression in mammalian cells.
“Currently, there are no universally accepted protocols for the generation of variegated antibody libraries or a selection thereof,” the authors write. One of the mutagenesis methods used in this paper is a novel combinatorial process that makes changes only in complementarity-determining regions. While both methods used had similar efficiency, the scientists report that “current methods for mutagenesis, antibody variant display, and screening for binders still need further optimization, especially as technologies for DNA synthesis and cell engineering become cheaper and more precise.”
Earlier this year, this group of scientists published a paper in Nature Biotechnology about a microfluidic technique to capture T cell receptors (TCRs) from a background of primary human T cells. They then build diverse TCR expression libraries, express them in mammalian cells, and screen for TCR candidates that might be useful for cell therapy. The high-throughput approach enables capturing and screening millions of TCR clonotypes.
To learn more about GigaGen’s fascinating work in antibody drug discovery — and how the BioXp® system has made a difference in their ability to prepare expression constructs — check out these papers as well:
Antibodies
Preferential Identification of Agonistic OX40 Antibodies by Using Cell Lysate to Pan Natively Paired, Humanized Mouse-Derived Yeast Surface Display Libraries
bioRxiv
Capturing and Recreating Diverse Antibody Repertoires as Multivalent Recombinant Polyclonal Antibody Drugs
mABs
A Natively Paired Antibody Library Yields Drug Leads with Higher Sensitivity and Specificity than a Randomly Paired Antibody Library