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Isolation of TGF-ß-neutralizing single-domain antibodies of predetermined epitope specificity using next-generation DNA sequencing.
Henry, Kevin A; Hussack, Greg; Collins, Cathy; Zwaagstra, John C; Tanha, Jamshid; MacKenzie, C Roger.
Afiliación
  • Henry KA; Human Health Therapeutics Portfolio, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario, CanadaK1A 0R6.
  • Hussack G; Human Health Therapeutics Portfolio, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario, CanadaK1A 0R6.
  • Collins C; Human Health Therapeutics Portfolio, National Research Council Canada, 6100 Royalmount Avenue, Montreal, Quebec, CanadaH4P 2R2.
  • Zwaagstra JC; Human Health Therapeutics Portfolio, National Research Council Canada, 6100 Royalmount Avenue, Montreal, Quebec, CanadaH4P 2R2.
  • Tanha J; Human Health Therapeutics Portfolio, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario, Canada K1A 0R6.
  • MacKenzie CR; School of Environmental Sciences, Ontario Agricultural College, University of Guelph, 50 Stone Road East, Guelph, Ontario, Canada N1G 2W1.
Protein Eng Des Sel ; 29(10): 439-443, 2016 10.
Article en En | MEDLINE | ID: mdl-27613412
The epitope specificity of therapeutic antibodies is often critical to their efficacy and mode of action. Here, we report the isolation of single-domain antibodies (sdAbs) against a pre-specified epitope of TGF-ß3: namely, the site of interaction between the cytokine and its cell-surface type II receptor. By panning a phage-displayed immune llama VhH library against TGF-ß3 using competitive elution with soluble dimeric type II receptor ectodomain in tandem with next-generation DNA sequencing, we identified several sdAbs that competed with the receptor for TGF-ß3 binding and neutralized TGF-ß3 in in vitro cellular assays. In contrast, all other sdAbs identified using conventional panning approaches (i.e., without regard to epitope specificity) did not target the site of receptor:cytokine interaction. We expect this strategy to be generally applicable for identifying epitope-specific sdAbs when binding reagents directed against the epitope of interest are available. The sdAbs identified here are of potential interest as cancer immunotherapeutics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Transformador beta / Análisis de Secuencia de ADN / Secuenciación de Nucleótidos de Alto Rendimiento / Anticuerpos de Dominio Único / Epítopos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Protein Eng Des Sel Asunto de la revista: BIOQUIMICA / BIOTECNOLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Transformador beta / Análisis de Secuencia de ADN / Secuenciación de Nucleótidos de Alto Rendimiento / Anticuerpos de Dominio Único / Epítopos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Protein Eng Des Sel Asunto de la revista: BIOQUIMICA / BIOTECNOLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido