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Round optimization for improved discovery of native bispecific antibodies

Author:
Gueneau, F., Ravn, U., Fischer, N.
Source:
Methods 2019 v.154 pp. 51-59
ISSN:
1046-2023
Subject:
antibodies, antigens, immunoglobulin G, peptide libraries
Abstract:
The assembly of bispecific antibodies (bsAb) that retain the structure of a standard IgG can be challenging as the correct pairing of the different heavy and light chains has to be ensured while unwanted side products kept to a minimum. The use of antibodies sharing a common chain facilitates assembly of such bsAb formats but requires additional efforts during the initial discovery phase. We have developed a native bsAb format called κλ body based on antibodies that, while being specific for different antigens, share the same heavy chain. Such antibodies can readily be isolated from antibody libraries incorporating a single VH combined with light chain diversity. However, in order to improve the discovery process of such fixed VH antibodies, we developed a method to optimize populations of light chains by recovering and shuffling CDRL3 sequences that have been enriched for antigen binding by phage display selection. This approach allowed for the isolation of a more diverse and potent panel of antibodies blocking the interaction between PD-1 and PD-L1 when compared to our standard in vitro selection approach, thus providing better building blocks for subsequent bsAb generation.
Agid:
6230135