Abstract 527: Isolation of large and diverse monoclonal antibody panels against the multipass membrane protein targets Kv1.3, P2X7, and Claudin 18.2

Monoclonal antibodies (MAbs) are a well-established treatment approach in oncology and other diseases. Nevertheless, multipass membrane proteins are largely inaccessible as MAb targets due to their poor expression, membrane-dependent structure, small extracellular regions, and high sequence conservation between humans and rodents. Integral Molecular9s MPS Antibody Discovery platform specifically addresses each of these challenges. Using this platform, we have isolated large and diverse panels of functional (agonist/antagonist) MAbs against targets including Claudin 18.2 and the ion channels P2X7 and Kv1.3. A key feature that enables the success of the platform is the use of divergent species for immunization. Chickens are immunized with a combination of DNA and Lipoparticles (high-concentration membrane proteins) to obtain high-titer immune responses against the native membrane protein. Our optimized phage-display protocols allow the isolation of large panels of MAbs against diverse epitopes. The MPS Antibody Discovery platform offers the potential for discovering MAbs against difficult targets in cancer with a success rate over 95%. Citation Format: Lewis J. Stafford, Sharon Willis, Joseph Rucker, Benjamin Doranz, Ross Chambers. Isolation of large and diverse monoclonal antibody panels against the multipass membrane protein targets Kv1.3, P2X7, and Claudin 18.2 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 527.