Screen Candidates And Select Better Leads For Developing Therapeutic Antibodies

As the demand for antibody therapies grows, so does the need for technologies that can accelerate the discovery of functional therapeutic antibodies, also known as lead molecules. However, discovering novel lead molecules requires methods to screen and rapidly down-select a diverse panel of antibodies.

Antibody-producing B lymphocytes (plasma cells) are leveraged to identify lead molecules, because each plasma cell secretes a unique functional antibody. The diverse range of secreted antibodies in the plasma cell population is referred to as the plasma cell repertoire. Antibody discovery using traditional hybridoma methods requires the immortalization of plasma cells by cell fusion, followed by a lengthy process of expansion and subcloning. This approach has been successful for finding lead molecules against simple targets but is limited when employed against difficult targets because the immortalization step often results in the death of >90% of plasma cells, and therefore leads to significant loss of the plasma cell diversity that is necessary for identifying rare, functional antibodies such as those against membrane targets. Other commercialized technologies, such as plasma cell cloning using flow cytometry or droplet encapsulation, may access more plasma cell diversity because they enrich the plasma cell population, however, none of these approaches provide insights into antibody function. As a result, nonfunctional or irrelevant hits are moved down the drug development pipeline to costly sequencing, gene synthesis, and bacterial cloning steps before functional confirmation using well plate-based assays.

In this application note, we will demonstrate how the Opto Plasma B Discovery 4.0 workflow can be used to access broad plasma cell diversity, rapidly down-select lead candidates with functional profiling, and sequence and re-express >1,000 functionally characterized antibodies for less than $100/molecule, in 1 week.