Engineering of antibodies and related receptors is most commonly performed using phage or yeast display, but mammalian cells are used for production. To streamline engineering of these and other membrane bound proteins, we developed a mammalian screening platform which allows for generation of large libraries and selection of variants with desirable characteristics in the manufacturing host. We have used this to engineer antibody Fab domains and showed that this platform can anticipate issues associated with glycosylation that would be missed by other screening platforms. We have also used it to identify human T cell receptors with low nanomolar affinities and increase TCR stability for expression as a soluble antibody-like molecule. Finally, we have used this platform to reduce tonic signaling issues in chimeric antigen receptors which may lead to increased persistence in vivo. Strategies to select for variants based on the desired protein activity as opposed to simple binding will be discussed.

Engineering in mammalian cells to streamline development of antibodies, antibody-like molecules and other proteins of therapeutic interest

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.