In vitro methods for screening libraries of antibody fragments (generally scFv or Fab) expressed as fusion proteins on the surface of bacteriophage or yeast cells are well-established. These strategies are noted for their high-throughput which increases the probability of finding antibodies that bind to the targets of interest. However, they are limited by the fact that selected antibodies do not undergo mammalian cell post-translational quality control, and thus do not have predictable expression or optimal biophysical properties in mammalian cell production systems.
Vaccinex has identified a need for a high-throughput, mammalian-based selection platform and has met this challenge by combining proprietary, large-scale library construction techniques with a novel vaccinia virus display method into one platform called ActivMAb®. ActivMAb® combines the throughput of phage and yeast display with mammalian-cell quality control in one platform to enable selection of full-length human IgG antibodies with that we believe have built-in manufacturability and favorable biophysical properties ideally suited for downstream development.
Substantial bottlenecks exist in the development of antibodies specific for GPCRs, ion channels and other multi-pass membrane proteins. One of these significant limitations is the difficulty in purifying conformationally active protein for antibody selection. Vaccinex has addressed this challenge by modifying our fusion protein technology to enable the direct incorporation of multipass membrane proteins such as GPCRs and ion channels into the viral membrane, a relatively clean environment in which to select antibodies without numerous false positives. This method is rapid, does not require any detergents or refolding, and can be applied to multiple different cell types in order to maximize protein expression. Antigen expressing virus can be readily purified and used for antibody selection.