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

Autor: Celso A. Reis, Karol Polom, Charlotte Welinder, Lena Danielsson, Nicolai Stuhr-Hansen, Stefan Mereiter, András Kovács, Ola Blixt, António Polónia, Bo Jansson, Christian Risinger, Franco Roviello, Nina Persson
Přispěvatelé: Instituto de Investigação e Inovação em Saúde
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Carbohydrate
glycosylation
Antigens
Tumor-Associated
Carbohydrate/chemistry
Tn antigen
Epitopes/immunology
Single-Chain Antibodies/chemistry
Biochemistry
Epitopes/chemistry
Stomach Neoplasms/metabolism
scFv
Epitope
Cell Line
Carcinoma/metabolism
03 medical and health sciences
Epitopes
Tn-antigen
Antigen
Stomach Neoplasms
Cell Line
Tumor
Humans
Antigens
Tumor-Associated
Carbohydrate
Antigens
Single-Chain Antibodies/immunology
Carcinoma/pathology
Tumor
Linear epitope
biology
gastric cancer
N-acetylgalactosamine (GalNAc)
solid-phase peptide synthesis
Carcinoma
Epitope Mapping
Single-Chain Antibodies
Chemistry
Tumor-Associated
Stomach Neoplasms/pathology
Molecular biology
3. Good health
030104 developmental biology
Epitope mapping
Antigens
Tumor-Associated
Carbohydrate/immunology
Cancer cell
biology.protein
Immunohistochemistry
Antibody
Zdroj: Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Popis: 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. This work was supported by the European Union, Seventh Framework Programme, GastricGlycoExplorer (GGE) initial training network [grant number 316929 to OB]; The Danish Research Council [grant number DFF-4005-00285 to OB]; Innovationsfonden in the framework of the EU-ERAsynBio-SynGlycTis project to OB; The EU-IMI 2 Joint Undertaking project EbolaMoDRAD [grant number 115843 to OB]; grants from Mrs. Berta Kamprad’s Foundation to CW; FEDER funds through the Operational Programme for Competitiveness Factors COMPETE [grant number FCOMP-01-0124-FEDER028188 to CR] and National Funds through FCT projects [grant numbers PEst-C/SAU/LA0003/2013, PTDC/BBB-EBI/0567/2014 to CR].
Databáze: OpenAIRE
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