On April 12, 2023 Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating neurodegenerative disease and cancer through the inhibition of SEMA4D reported a new publication in the March 30, 2023 issue of Nature Communications describing a novel way that the ActivMab platform can be used for functional studies and drug discovery of the "hard to drug" class of membrane-associated G protein-coupled receptors (GPCRs) and ion channels (Press release, Vaccinex, APR 12, 2023, View Source [SID1234630010]).
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The Nature Communications article, titled "A Vaccinia-based system for directed evolution of GPCRs in mammalian cells" provides an overview of how Vaccinex and its collaborators at the University of Zurich created an elegant system to make highly diverse libraries of functional GPCR variants and to enrich for variants with improved expression levels and stability while maintaining functional aspects of GPCR signaling. GPCRs are a very important class of drug targets because of their critical role in physiological processes. However, low expression levels and dependence on the mammalian membrane environment for conformational stability and function make them difficult targets for drug selection. The authors demonstrate that the ActivMAb technology overcomes these limitations by engineering directed protein evolution libraries in a mammalian signaling environment allowing GPCR expression that is amenable to structural studies. This novel application could be utilized to decipher the functional properties of GPCR for drug discovery or to incorporate GPCR membrane receptors into novel drug screening assays.
"Vaccinex is very pleased that this pioneering work by our scientists in collaboration with the group of Dr. Andreas Plückthun of the University of Zurich has been published in Nature Communications," said Ernest Smith, Ph.D., Sr. Vice President Research and Chief Scientific Officer. "GPCRs are a very important class of drug targets because of their critical role in physiological processes. The complex biophysical properties of these important targets embedded in the cell membrane can make them "difficult to drug". We believe that our novel directed evolution system will allow us to generate improved variants of any GPCR in a mammalian signaling system, better enabling us and our partners to study the functional properties of these complex receptors and develop new and valuable drugs against these important targets. We believe this new technology application will further enhance our ActivMab offering, and we look forward to sharing it with our partners."
About ActivMAb
Vaccinex has developed a proprietary mammalian cell-based antibody discovery platform with unique capabilities for multi-pass membrane targets such as G-protein-coupled receptors (GPCRs). The ActivMAb technology has five main applications: complex membrane antigen presentation, antibody or antigen discovery, directed evolution and protein optimization. The first clinical candidate selected through use of this technology (SRF114, a fully human monoclonal antibody targeting CCR8 for the potential treatment of solid tumors), recently entered development in a Phase 1/2 study sponsored by our licensee, Surface Oncology. Vaccinex has entered into multiple antibody discovery collaborations with leading biopharmaceutical companies.