Synthesis of bispecific antibodies using genetically encoded unnatural amino acids.
Bispecific antibodies were constructed using genetically encoded unnatural amino acids with orthogonal chemical reactivity. A two-step process afforded homogeneous products in excellent yield. Using this approach, we synthesized an anti-HER2/anti-CD3 bispecific antibody, which efficiently cross-linked HER2+ cells and CD3+ cells. In vitro effector-cell mediated cytotoxicity was observed at picomolar concentrations.
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Chan Hyuk
CH
Kim
Jun Y
JY
Axup
Anna
A
Dubrovska
Stephanie A
SA
Kazane
Benjamin A
BA
Hutchins
Erik D
ED
Wold
Vaughn V
VV
Smider
Peter G
PG
Schultz
D000596:Amino Acids / Q000737:chemistry*; D018033:Antibodies, Bispecific / Q000737:chemistry* / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008958:Models, Molecular; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*
D000596:Amino Acids; D018033:Antibodies, Bispecific; D017252:CD3 Complex; D018719:Erb-b2 Receptor Tyrosine Kinases