Human Antibody Bispecifics through Phage Display Selection

Ansha Luthra; David B Langley; Peter Schofield; Jennifer Jackson; Mahmoud Abdelatti; Romain Rouet; Damien Nevoltris; Ohan Mazigi; Ben Crossett; Mary Christie; Daniel Christ

doi:10.1021/acs.biochem.9b00037

Human Antibody Bispecifics through Phage Display Selection

Biochemistry. 2019 Apr 2;58(13):1701-1704. doi: 10.1021/acs.biochem.9b00037. Epub 2019 Mar 22.

Authors

Ansha Luthra^{1

2}, David B Langley¹, Peter Schofield^{1

2}, Jennifer Jackson¹, Mahmoud Abdelatti¹, Romain Rouet¹, Damien Nevoltris¹, Ohan Mazigi^{1

2}, Ben Crossett³, Mary Christie⁴, Daniel Christ^{1

2}

Affiliations

¹ Garvan Institute of Medical Research , 384 Victoria Road , Darlinghurst, Sydney , New South Wales 2010 , Australia.
² Faculty of Medicine, St Vincent's Clinical School , The University of New South Wales , Darlinghurst, Sydney , New South Wales 2010 , Australia.
³ Sydney Mass Spectrometry, Charles Perkins Centre , The University of Sydney , Camperdown, Sydney , New South Wales 2006 , Australia.
⁴ Victor Chang Cardiac Research Institute , 405 Liverpool Street , Darlinghurst , New South Wales 2010 , Australia.

PMID: 30900875
DOI: 10.1021/acs.biochem.9b00037

Abstract

We developed a repertoire approach to generate human antibody bispecifics. Using phage display selection of antibody heavy chains in the presence of a competitor light chain and providing a cognate light chain with an affinity handle, we identified mutations that prevent heavy/light chain mispairing. The strategy allows for the selection of human antibody chains that autonomously assemble into bispecifics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Antibodies, Bispecific / chemistry
Antibodies, Bispecific / immunology*
Antibody Affinity
Humans
Immunoglobulin Heavy Chains / chemistry
Immunoglobulin Heavy Chains / immunology
Immunoglobulin Light Chains / chemistry
Immunoglobulin Light Chains / immunology
Models, Molecular
Peptide Library*

Substances

Antibodies, Bispecific
Immunoglobulin Heavy Chains
Immunoglobulin Light Chains
Peptide Library