RESUMO

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.

Assuntos

Anticorpos Monoclonais/farmacocinética , Antígeno Carcinoembrionário/imunologia , Fragmentos de Imunoglobulinas/farmacologia , Neoplasias/metabolismo , Proteínas Recombinantes/farmacocinética , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Linhagem Celular Tumoral , Clonagem Molecular , Escherichia coli/genética , Feminino , Humanos , Fragmentos de Imunoglobulinas/química , Fragmentos de Imunoglobulinas/imunologia , Radioisótopos do Iodo , Camundongos , Camundongos Nus , Dados de Sequência Molecular , Transplante de Neoplasias , Neoplasias/diagnóstico por imagem , Neoplasias/imunologia , Radioimunodetecção , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia