An anti-P-gp/anti-CD3 bispecific antibody cytotoxic to human multidrug resistant KB cells / 中华肿瘤杂志
Chinese Journal of Oncology
;
(12): 653-656, 2005.
Artigo
em Chinês
| WPRIM
| ID: wpr-358544
ABSTRACT
<p><b>OBJECTIVE</b>To study the specific cytotoxicity mediated by anti-P-gp/anti-CD(3) diabodies in multidrug resistant solid tumor using P-gp as target.</p><p><b>METHODS</b>The anti-P-gp/anti-CD(3) diabodies were secreted from E. coli strain 16C9 containing the expression plasmid PAYZDCP, grown at 30 degrees C in a shaker flask; the diabodies were purified by affinity chromatography and identified by SDS-PAGE; the effect of the anti-P-gp/anti-CD(3) diabody mediated lysis of P-gp-expressing tumor cells was assayed by (51)Cr release assay in vitro, and by human KB nude mouse xenograft models in vivo.</p><p><b>RESULTS</b>The diabodies were generated by bacteria as a soluble functional form and purified by one-step affinity chromatography with a yield > 4 mg/L culture medium. In (51)Cr release assay, the diabodies targeted human activated T cells to lyse P-gp(+)-KB/MDR cells in a dose-dependent manner. It suggested that the diabody was able to induce an efficient lysis of the target cells by human T cells in vitro. When combined with activated human T cells, the diabody significantly inhibited the growth of KB/MDR, but had no effect on KB xenografts.</p><p><b>CONCLUSION</b>The anti-P-gp/anti-CD(3) bispecific antibody is a potent agent for targeting human T lymphocytes to lyse solid tumor cells overexpressing P-gp in vitro and in vivo.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Terapêutica
/
Proteínas Recombinantes
/
Células KB
/
Linfócitos T Citotóxicos
/
Engenharia de Proteínas
/
Complexo CD3
/
Anticorpos Biespecíficos
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
/
Resistência a Múltiplos Medicamentos
/
Resistencia a Medicamentos Antineoplásicos
Limite:
Animais
/
Feminino
/
Humanos
Idioma:
Chinês
Revista:
Chinese Journal of Oncology
Ano de publicação:
2005
Tipo de documento:
Artigo
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