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Cancer Res ; 64(3): 781-8, 2004 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-14871799

RESUMO

Analysis of human colorectal cancer specimens revealed overexpression of the EphB2 receptor tyrosine kinase. Monoclonal antibodies (MAbs) to extracellular sequence of EphB2 were raised and tested for activity against colorectal cancer cells. One of the MAbs, 2H9, effectively blocked the interaction of ephB2 with ephrin ligands and inhibited the resulting autophosphorylation of the receptor. However, this antibody did not affect the proliferation of cancer cells expressing ephB2. Immunocytochemical analysis revealed rapid internalization of the MAb 2H9 on binding ephB2, suggesting that target-dependent cell killing could be achieved with an antibody-drug conjugate. When MAb 2H9 was conjugated to monomethylauristatin E through a cathepsin B-cleavable linker, it specifically killed ephB2-expressing cancer cells in vitro and in vivo. Our results suggest that ephB2 is an attractive target for immunoconjugate cancer therapy.


Assuntos
Adenocarcinoma/terapia , Anticorpos Monoclonais/farmacologia , Neoplasias do Colo/terapia , Imunotoxinas/farmacologia , Receptor EphB2/antagonistas & inibidores , Adenocarcinoma/enzimologia , Adenocarcinoma/imunologia , Animais , Anticorpos Monoclonais/imunologia , Linhagem Celular Tumoral , Neoplasias do Colo/enzimologia , Neoplasias do Colo/imunologia , Feminino , Humanos , Imunotoxinas/imunologia , Camundongos , Camundongos Nus , Receptor EphB2/biossíntese , Receptor EphB2/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
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