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Monoclonal antibodies toward different Tn-amino acid backbones display distinct recognition patterns on human cancer cells. Implications for effective immuno-targeting of cancer.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2013 Jun; Vol. 62 (6), pp. 1107-22. Date of Electronic Publication: 2013 Apr 21. - Publication Year :
- 2013
-
Abstract
- The Tn antigen (GalNAcα-O-Ser/Thr) is a well-established tumor-associated marker which represents a good target for the design of anti-tumor vaccines. Several studies have established that the binding of some anti-Tn antibodies could be affected by the density of Tn determinant or/and by the amino acid residues neighboring O-glycosylation sites. In the present study, using synthetic Tn-based vaccines, we have generated a panel of anti-Tn monoclonal antibodies. Analysis of their binding to various synthetic glycopeptides, modifying the amino acid carrier of the GalNAc(*) (Ser* vs Thr*), showed subtle differences in their fine specificities. We found that the recognition of these glycopeptides by some of these MAbs was strongly affected by the Tn backbone, such as a S*S*S* specific MAb (15G9) which failed to recognize a S*T*T* or a T*T*T* structure. Different binding patterns of these antibodies were also observed in FACS and Western blot analysis using three human cancer cell lines (MCF-7, LS174T and Jurkat). Importantly, an immunohistochemical analysis of human tumors (72 breast cancer and 44 colon cancer) showed the existence of different recognition profiles among the five antibodies evaluated, demonstrating that the aglyconic part of the Tn structure (Ser vs Thr) plays a key role in the anti-Tn specificity for breast and colon cancer detection. This new structural feature of the Tn antigen could be of important clinical value, notably due to the increasing interest of this antigen in anticancer vaccine design as well as for the development of anti-Tn antibodies for in vivo diagnostic and therapeutic strategies.
- Subjects :
- Adult
Aged
Aged, 80 and over
Amino Acid Sequence
Animals
Antibodies, Monoclonal metabolism
Antibody Specificity immunology
Antigens, Tumor-Associated, Carbohydrate chemistry
Antigens, Tumor-Associated, Carbohydrate metabolism
Biomarkers, Tumor
Breast Neoplasms immunology
Breast Neoplasms metabolism
Breast Neoplasms pathology
Cell Line, Tumor
Colonic Neoplasms immunology
Colonic Neoplasms metabolism
Colonic Neoplasms pathology
Female
Glycopeptides chemistry
Glycopeptides metabolism
Humans
Male
Mice
Middle Aged
Neoplasm Staging
Neoplasms metabolism
Neoplasms pathology
Protein Binding immunology
Antibodies, Monoclonal immunology
Antigens, Tumor-Associated, Carbohydrate immunology
Glycopeptides immunology
Neoplasms immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0851
- Volume :
- 62
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 23604173
- Full Text :
- https://doi.org/10.1007/s00262-013-1425-7