Differential tumor-targeting abilities of three single-domain antibody formats

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DOIResolve DOI: http://doi.org/10.1016/j.canlet.2009.08.003
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TypeArticle
Journal titleCancer Letters
Volume289
Issue1
Pages8190; # of pages: 10
AbstractThe large molecular size of antibody drugs is considered one major factor preventing them from becoming more efficient therapeutics. Variable regions of heavy chain antibodies (HCAbs), or single-domain antibodies (sdAbs), are ideal building blocks for smaller antibodies due to their molecular size and enhanced stability. In the search for better antibody formats for in vivo imaging and/or therapy of cancer, three types of sdAb-based molecules directed against epidermal growth factor receptor (EGFR) were constructed, characterized and tested. Eleven sdAbs were isolated from a phage display library constructed from the sdAb repertoire of a llama immunized with a variant of EGFR. A pentameric sdAb, or pentabody, V2C-EG2 was constructed by fusing one of the sdAbs, EG2, to a pentamerization protein domain. A chimeric HCAb (cHCAb), EG2-hFc, was constructed by fusing EG2 to the fragment crystallizable (Fc) of human IgG1. Whereas EG2 and V2C-EG2 localized mainly in the kidneys after i.v. injection, EG2-hFc exhibited excellent tumor accumulation, and this was largely attributed to its long serum half life, which is comparable to that of IgGs. The moderate size (~80 kDa) and intact human Fc make HCAbs a unique antibody format which may outperform whole IgGs as imaging and therapeutic reagents.
Publication date
LanguageEnglish
AffiliationNRC Biotechnology Research Institute; NRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedYes
NRC number52735
NPARC number12429639
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Record identifier22299b90-e406-4dcc-b913-27edcdd1cb17
Record created2009-10-27
Record modified2016-05-09
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