1. Generation of Fcabs targeting human and murine LAG-3 as building blocks for novel bispecific antibody therapeutics.
- Author
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Everett, Katy L., Kraman, Matthew, Wollerton, Francisca P.G., Zimarino, Carlo, Kmiecik, Katarzyna, Gaspar, Miguel, Pechouckova, Sarka, Allen, Natalie L., Doody, Jacqueline F., and Tuna, Mihriban
- Subjects
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BISPECIFIC antibodies , *CARRIER proteins , *IMMUNOGLOBULINS , *CANCER treatment , *T cells - Abstract
Highlights • Phage display was used to generate Fcabs targeting human and murine LAG-3. • These Fcabs block LAG-3 binding to its target and induce activity in a T cell assay. • Fcab properties are maintained when they are included in bispecific antibodies. Abstract The immunoglobulin superfamily protein lymphocyte-activation gene 3 (LAG-3) participates in immune suppression and has been identified as a suitable target for cancer therapies. In order to generate bispecific antibodies targeting LAG-3, Fcabs (Fc-region with antigen binding) targeting human and murine LAG-3 were generated from phage libraries. These Fcabs bind to LAG-3, inhibiting its interaction with MHC class II, and induce IL-2 production in a T cell assay. Bispecific antibodies, known as mAb2, were produced by replacing the Fc region of a monoclonal antibody with Fcab sequences in the CH3 domain. mAb2 containing anti-LAG-3 Fcabs have mAb-like biophysical characteristics and retain LAG-3 binding and functional activity. mAb2 can thus be generated using multiple Fabs to investigate bispecific parings and develop novel therapeutics. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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