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Epitope mapping of a new anti-Tn antibody detecting gastric cancer cells

Persson, Nina; Stuhr-Hansen, Nicolai; Risinger, Christian; Mereiter, Stefan; Polónia, António; Polom, Karol; Kovács, András LU ; Roviello, Franco; Reis, Celso A. and Welinder, Charlotte LU , et al. (2017) In Glycobiology 27(7). p.635-645
Abstract

Here, we introduce a novel scFv antibody, G2-D11, specific for two adjacent Tn-antigens (GalNAc- Ser/Thr) binding equally to three dimeric forms of the epitope, Ser-Thr, Thr-Thr and Thr-Ser. Compared to other anti-Tn reagents, the binding of G2-D11 is minimally influenced by the peptide structure, which indicates a high degree of carbohydrate epitope dominance and a low influence from the protein backbone. With a high affinity (KDapp = 1.3 × 10-8 M) and no cross-reactivity to either sialyl-Tn epitope or blood group A antigens, scFv G2-D11 is an excellent candidate for a well-defined anti-Tn-antigen reagent. Detailed immunohistochemical evaluation of tissue sections from a cohort of 80 patients with gastric... (More)

Here, we introduce a novel scFv antibody, G2-D11, specific for two adjacent Tn-antigens (GalNAc- Ser/Thr) binding equally to three dimeric forms of the epitope, Ser-Thr, Thr-Thr and Thr-Ser. Compared to other anti-Tn reagents, the binding of G2-D11 is minimally influenced by the peptide structure, which indicates a high degree of carbohydrate epitope dominance and a low influence from the protein backbone. With a high affinity (KDapp = 1.3 × 10-8 M) and no cross-reactivity to either sialyl-Tn epitope or blood group A antigens, scFv G2-D11 is an excellent candidate for a well-defined anti-Tn-antigen reagent. Detailed immunohistochemical evaluation of tissue sections from a cohort of 80 patients with gastric carcinoma showed in all cases positive tumor cells. The observed staining was localized to the cytoplasm and in some cases to the membrane, whereas the surrounding tissue was completely negative demonstrating the usefulness of the novel Tn-antigen binding antibody.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
gastric cancer, glycosylation, N-acetylgalactosamine (GalNAc), scFv, solid-phase peptide synthesis, Tn-antigen
in
Glycobiology
volume
27
issue
7
pages
11 pages
publisher
Oxford University Press
external identifiers
  • scopus:85021721636
  • wos:000404883300006
ISSN
0959-6658
DOI
10.1093/glycob/cwx033
language
English
LU publication?
yes
id
e34e6645-e95c-4465-a522-6fdd6be1f16c
date added to LUP
2017-07-18 14:54:51
date last changed
2018-01-07 12:12:10
@article{e34e6645-e95c-4465-a522-6fdd6be1f16c,
  abstract     = {<p>Here, we introduce a novel scFv antibody, G2-D11, specific for two adjacent Tn-antigens (GalNAc- Ser/Thr) binding equally to three dimeric forms of the epitope, Ser-Thr, Thr-Thr and Thr-Ser. Compared to other anti-Tn reagents, the binding of G2-D11 is minimally influenced by the peptide structure, which indicates a high degree of carbohydrate epitope dominance and a low influence from the protein backbone. With a high affinity (K<sub>Dapp</sub> = 1.3 × 10<sup>-8</sup> M) and no cross-reactivity to either sialyl-Tn epitope or blood group A antigens, scFv G2-D11 is an excellent candidate for a well-defined anti-Tn-antigen reagent. Detailed immunohistochemical evaluation of tissue sections from a cohort of 80 patients with gastric carcinoma showed in all cases positive tumor cells. The observed staining was localized to the cytoplasm and in some cases to the membrane, whereas the surrounding tissue was completely negative demonstrating the usefulness of the novel Tn-antigen binding antibody.</p>},
  author       = {Persson, Nina and Stuhr-Hansen, Nicolai and Risinger, Christian and Mereiter, Stefan and Polónia, António and Polom, Karol and Kovács, András and Roviello, Franco and Reis, Celso A. and Welinder, Charlotte and Danielsson, Lena and Jansson, Bo and Blixt, Ola},
  issn         = {0959-6658},
  keyword      = {gastric cancer,glycosylation,N-acetylgalactosamine (GalNAc),scFv,solid-phase peptide synthesis,Tn-antigen},
  language     = {eng},
  month        = {07},
  number       = {7},
  pages        = {635--645},
  publisher    = {Oxford University Press},
  series       = {Glycobiology},
  title        = {Epitope mapping of a new anti-Tn antibody detecting gastric cancer cells},
  url          = {http://dx.doi.org/10.1093/glycob/cwx033},
  volume       = {27},
  year         = {2017},
}