Prolonged in vivo residence times of antibody fragments associated with albumin.
Antibody fragments can be expressed at a high level in microbial systems, but they may have limited therapeutic value because they are rapidly eliminated from the body. We demonstrate here that site-specific conjugation or binding of bacterially derived Fab' to the long-lived protein serum albumin allows full retention of the antibody's binding characteristics while imparting the albumin's longevity in vivo. In rats the area under the curve for Fab' conjugated to rat serum albumin was 17-fold greater than for the control of Fab' conjugated to cysteine. Again, a bispecific F(ab')(2) with specificity for rat serum albumin showed an area under the curve about 8-fold greater than did a F(ab')(2) without specificity to albumin. Genetic fusions of scFv to albumin were similarly long-lived and could be expressed in yeast to provide the basis of a cost-effective production system.
Smith
B J
BJ
Celltech R and D Ltd, 208 Bath Road, Slough, Berks SL1 4EN, UK. bsmith@celltech.co.uk
Popplewell
A
A
Athwal
D
D
Chapman
A P
AP
Heywood
S
S
West
S M
SM
Carrington
B
B
Nesbitt
A
A
Lawson
A D
AD
Antoniw
P
P
Eddelston
A
A
Suitters
A
A
D000818:Animals; D000907:Antibodies, Bacterial / Q000737:chemistry; D018033:Antibodies, Bispecific / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003432:Cross-Linking Reagents / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D007128:Immunoglobulin Fragments / Q000008:administration & dosage / Q000737:chemistry*; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics; D012709:Serum Albumin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
D000907:Antibodies, Bacterial; D018033:Antibodies, Bispecific; D003432:Cross-Linking Reagents; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin