RESUMO
INTRODUCTION: The insulin-like growth factor type 1 (IGF-1) receptor contributes importantly to transformation and survival of tumor cells both in vitro and in vivo, and selective antagonists of the IGF-1 receptor (IGF-1R) activity represent an attractive experimental approach for human cancer therapy. METHODS: Using a phage display library, we identified several high-affinity fully human monoclonal antibodies with inhibitory activity against both human and rodent IGF.1Rs. RESULTS: These candidate therapeutic antibodies recognized several distinct epitopes and effectively blocked ligand-mediated receptor signal transduction and cellular proliferation in vitro. They also induced IGF-1R downregulation and catabolism following antibody-mediated endocytosis. These antibodies exhibited activity against human, primate, and rodent IGF-1Rs, and dose-dependently inhibited the growth of established human tumors in nude mice. CONCLUSION: These fully human antibodies therefore have the potential to provide an effective anti-tumor biological therapy in the human clinical setting.
Assuntos
Anticorpos Monoclonais/farmacologia , Proliferação de Células/efeitos dos fármacos , Receptor IGF Tipo 1/imunologia , Células 3T3 , Animais , Afinidade de Anticorpos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Regulação para Baixo , Mapeamento de Epitopos , Humanos , Camundongos , Camundongos Nus , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transfecção , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/patologiaRESUMO
Binding of antibodies to oligomeric envelope glycoprotein of R5-tropic primary isolates of human immunodeficiency virus type 1 (HIV-1) was studied by flow cytometry using sera from HIV-1 vaccine recipients and clade B and C HIV-1-infected patients, and monoclonal and polyclonal antibodies to neutralizing epitopes of HIV-1. Vaccine recipients received recombinant canarypox virus vaccine expressing HIV-1 gene products, and SF-2 recombinant gp120 subunit vaccine. Anti-gp120 neutralizing antibodies including human monoclonal antibody 2G12 and goat polyclonal anti-serum to V3 loop peptide [peptide T1-SP10MN(A)] bound to HIV-1-infected cells. Sera from vaccine recipients bound to HIV-1-infected cells, but at levels lower than did infected patient sera.
