Bispecific antibody generated with sortase and click chemistry has broad antiinfluenza virus activity.
Bispecific antibodies have therapeutic potential by expanding the functions of conventional antibodies. Many different formats of bispecific antibodies have meanwhile been developed. Most are genetic modifications of the antibody backbone to facilitate incorporation of two different variable domains into a single molecule. Here, we present a bispecific format where we have fused two full-sized IgG antibodies via their C termini using sortase transpeptidation and click chemistry to create a covalently linked IgG antibody heterodimer. By linking two potent anti-influenza A antibodies together, we have generated a full antibody dimer with bispecific activity that retains the activity and stability of the two fusion partners.
AIMM Therapeutics, 1105 BA Amsterdam, The Netherlands;
Koen
K
Wagner
AIMM Therapeutics, 1105 BA Amsterdam, The Netherlands;
Mark J
MJ
Kwakkenbos
AIMM Therapeutics, 1105 BA Amsterdam, The Netherlands;
Yvonne B
YB
Claassen
AIMM Therapeutics, 1105 BA Amsterdam, The Netherlands;
Kelly
K
Maijoor
AIMM Therapeutics, 1105 BA Amsterdam, The Netherlands;
Martino
M
Böhne
Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
Koenraad F
KF
van der Sluijs
Whitehead Institute for Biomedical Research, Cambridge, MA 02142; and.
Martin D
MD
Witte
Department of Virology, Central Veterinary Institute, Wageningen University and Research Centre, 8200 AB Lelystad, The Netherlands.
Diana J
DJ
van Zoelen
Department of Virology, Central Veterinary Institute, Wageningen University and Research Centre, 8200 AB Lelystad, The Netherlands.
Lisette A
LA
Cornelissen
AIMM Therapeutics, 1105 BA Amsterdam, The Netherlands;
Tim
T
Beaumont
AIMM Therapeutics, 1105 BA Amsterdam, The Netherlands;
Arjen Q
AQ
Bakker
Whitehead Institute for Biomedical Research, Cambridge, MA 02142; and.
Hidde L
HL
Ploegh
AIMM Therapeutics, 1105 BA Amsterdam, The Netherlands; hspits@aimmtherapeutics.com.
Hergen
H
Spits
D018033:Antibodies, Bispecific / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology; D001402:B-Lymphocytes / Q000821:virology; D015153:Blotting, Western; D002478:Cells, Cultured; D057930:Click Chemistry; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D009980:Influenza A virus / Q000145:classification / Q000276:immunology*; D020349:Surface Plasmon Resonance
D018033:Antibodies, Bispecific
antibody engineering; immunotherapy; influenza