Generation of Fcabs targeting human and murine LAG-3 as building blocks for novel bispecific antibody therapeutics

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.