Isolation and characterization of camelid single-domain antibodies against HER2.

Autor: Hussack G; Human Health Therapeutics Research Centre, National Research Council Canada, 100 Sussex Drive, Ottawa, ON, K1A 0R6, Canada., Raphael S; Human Health Therapeutics Research Centre, National Research Council Canada, 100 Sussex Drive, Ottawa, ON, K1A 0R6, Canada., Lowden MJ; Human Health Therapeutics Research Centre, National Research Council Canada, 100 Sussex Drive, Ottawa, ON, K1A 0R6, Canada., Henry KA; Human Health Therapeutics Research Centre, National Research Council Canada, 100 Sussex Drive, Ottawa, ON, K1A 0R6, Canada. kevin.henry@nrc-cnrc.gc.ca.
Jazyk: angličtina
Zdroj: BMC research notes [BMC Res Notes] 2018 Dec 05; Vol. 11 (1), pp. 866. Date of Electronic Publication: 2018 Dec 05.
DOI: 10.1186/s13104-018-3955-8
Abstrakt: Objective: To isolate and characterize novel high-affinity llama single-domain antibodies against human HER2.
Results: We immunized a llama with human HER2, constructed a phage-displayed V H H library from the lymphocytes of the animal, and isolated six unique HER2-specific V H Hs by panning. All six V H Hs were unique at the amino acid level and were clonally unrelated, as reflected by their distinct CDR3 lengths. All six V H Hs recognized recombinant human HER2 ectodomain with monovalent affinities ranging from 1 to 51 nM, had comparable affinities for cynomolgus monkey HER2, and bound HER2 + SKOV3 cells by flow cytometry. Three of the V H Hs recognized recombinant murine HER2 with no loss of affinity compared with human and cynomolgus monkey HER2. The V H Hs recognized three major epitopes on HER2 (including one conserved across the human, simian and murine orthologues), all of which were distinct from that of trastuzumab. These V H Hs may be useful in the design of modular cancer immunotherapeutics.
Databáze: MEDLINE
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