Poster Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

Abstract:

Therapeutic antibodies are among the fastest growing class of biopharmaceuticals. This advance has been enabled by rapid advancements in protein engineering technologies, which has allowed for various antibody formats, altering the traditional structure of the IgG molecule[1]. One such format is bispecific antibodies, which have been engineered to possess two different antigen-binding specificities at either end of the Fab arms. Among the many novel uses for this format, is the capability to target two growth factor receptors simultaneously or targeting a tumor specific receptor whilst simultaneously recruiting a T cell response to the site [2]. Unfortunately current methods used for producing bispecific antibodies are suboptimal and yield non-functional antibodies due to misassembled chains[3]. Here we outline strategies to overcome chain mis assembly by a combination of phage display selection, mutagenesis and x-ray crystallography. 

References:

1. Carter, P.J., Potent antibody therapeutics by design.Nature Reviews Immunology, 2006. 6(5): p. 343-357.
2. Lum, L. and A. Thakur, Targeting T Cells with Bispecific Antibodies for Cancer Therapy.BioDrugs, 2011. 25(6): p. 365-379.

3. Rouet, R. and D. Christ (2014). "Bispecific antibodies with native chain structure." Nature biotechnology 32(2): 136-137.