A multivalent recombinant antibody fragment specific for carcinoembryonic antigen.
In the present paper we report the development of a bivalent scFv (single-chain Fv) antibody fragment, starting from a mouse mAb (monoclonal antibody) specific for CEA (carcinoembryonic antigen) that has received approval for in vivo radioimmunodiagnosis in humans. The diabody is well expressed in Escherichia coli, is easily purified by a combination of immobilized metal ion affinity chromatography and gel filtration and exhibits high affinity and specificity for CEA, comparable with those of the original mAb. Biodistribution experiments in athymic nude mice transplanted with human CEA+ cancer cells showed that the 125I-labelled diabody preferentially localizes in the tumour tissue and that retention is still high 48 h after injection. The diabody can be advantageous for some in vivo tumour targeting applications, due to the faster clearance derived from its smaller molecular mass.
Perez
Lincidio
L
Recombinant Antibody Group, Cancer Research Department, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba.
Ayala
Marta
M
Pimentel
Gilmara
G
Bell
Hanssel
H
Canaán-Haden
Leonardo
L
Bequet
Mónica
M
González
Luis Javier
LJ
Miranda
Marlen
M
Ravelo
Rolando
R
Roque
Lourdes
L
Acevedo
Boris
B
Oliva
Juan P
JP
Gavilondo
Jorge V
JV
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D016719:Radioimmunodetection; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics*
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007128:Immunoglobulin Fragments; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins