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Biochem Biophys Res Commun ; 280(2): 548-52, 2001 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-11162553

RESUMO

The display of human antibody repertoire on the cell surface of the filamentous bacteriophage has offered a novel strategy for selecting antibodies to a diverse range of purified targets. However, the selection of antibodies with biological functions has not yet been fully investigated. To select phage antibodies with therapeutic potential, a synthetic human single chain Fv (scFv) phage antibody library was panned on whole premyelocytic leukemia cell line (HL60). Phages binding to common receptors and undesirable phages were subtracted by incubating the library with human glioma cells. High affinity binding phages to HL60 cells were enriched by fluorescence-activated cell sorting. After the 6th round of selection, 50% of the selected phage antibodies showed significant binding to HL60 cells, whereas none of the analyzed phage antibodies bound to human pre-B cells (Nalm-6). In addition to binding, one scFv antibody inhibited HL60 cell proliferation by 90% compared to irrelevant scFv antibodies. Taken together the data demonstrate that specific scFv antibodies with biological functions can be isolated by using whole cells as affinity matrix.


Assuntos
Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/imunologia , Biblioteca de Peptídeos , Especificidade de Anticorpos/imunologia , Linfócitos B/imunologia , Western Blotting , Divisão Celular/efeitos dos fármacos , Citometria de Fluxo , Glioma/imunologia , Células HL-60 , Humanos , Fragmentos Fab das Imunoglobulinas/genética , Fragmentos Fab das Imunoglobulinas/farmacologia , Leucemia Mieloide/patologia , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/patologia , Células Tumorais Cultivadas
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