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

Nina Persson; Nicolai Stuhr-Hansen; Christian Risinger; Stefan Mereiter; António Polónia; Karol Polom; András Kovács; Franco Roviello; Celso A. Reis; Charlotte Welinder; Lena Danielsson; Bo Jansson; Ola Blixt

doi:10.1093/glycob/cwx033

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

Nina Persson, Nicolai Stuhr-Hansen, Christian Risinger, Stefan Mereiter, António Polónia, Karol Polom, András Kovács, Franco Roviello, Celso A. Reis, Charlotte Welinder, Lena Danielsson, Bo Jansson, Ola Blixt

Research output: Contribution to journal › Article › peer-review

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 (K_Dapp = 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.

Original language	English
Pages (from-to)	635-645
Number of pages	11
Journal	Glycobiology
Volume	27
Issue number	7
DOIs	https://doi.org/10.1093/glycob/cwx033
Publication status	Published - 2017 Jul 1

Subject classification (UKÄ)

Cell and Molecular Biology
Cancer and Oncology

Free keywords

gastric cancer
glycosylation
N-acetylgalactosamine (GalNAc)
scFv
solid-phase peptide synthesis
Tn-antigen

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/glycob/cwx033

Cite this

@article{e34e6645e95c4465a5226fdd6be1f16c,

title = "Epitope mapping of a new anti-Tn antibody detecting gastric cancer cells",

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 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.",

keywords = "gastric cancer, glycosylation, N-acetylgalactosamine (GalNAc), scFv, solid-phase peptide synthesis, Tn-antigen",

author = "Nina Persson and Nicolai Stuhr-Hansen and Christian Risinger and Stefan Mereiter and Ant{\'o}nio Pol{\'o}nia and Karol Polom and Andr{\'a}s Kov{\'a}cs and Franco Roviello and Reis, {Celso A.} and Charlotte Welinder and Lena Danielsson and Bo Jansson and Ola Blixt",

year = "2017",

month = jul,

day = "1",

doi = "10.1093/glycob/cwx033",

language = "English",

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pages = "635--645",

journal = "Glycobiology",

issn = "0959-6658",

publisher = "Oxford University Press",

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TY - JOUR

T1 - Epitope mapping of a new anti-Tn antibody detecting gastric cancer cells

AU - Persson, Nina

AU - Stuhr-Hansen, Nicolai

AU - Risinger, Christian

AU - Mereiter, Stefan

AU - Polónia, António

AU - Polom, Karol

AU - Kovács, András

AU - Roviello, Franco

AU - Reis, Celso A.

AU - Welinder, Charlotte

AU - Danielsson, Lena

AU - Jansson, Bo

AU - Blixt, Ola

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - gastric cancer

KW - glycosylation

KW - N-acetylgalactosamine (GalNAc)

KW - scFv

KW - solid-phase peptide synthesis

KW - Tn-antigen

U2 - 10.1093/glycob/cwx033

DO - 10.1093/glycob/cwx033

M3 - Article

C2 - 28419225

AN - SCOPUS:85021721636

SN - 0959-6658

VL - 27

SP - 635

EP - 645

JO - Glycobiology

JF - Glycobiology

IS - 7

ER -

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

Abstract

Subject classification (UKÄ)

Free keywords

UN SDGs

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