Monoclonal antibodies toward different Tn-amino acid backbones display distinct recognition patterns on human cancer cells. Implications for effective immuno-targeting of cancer

Autor: Luis Ubillos, Claude Leclerc, Otto Pritsch, Andrea Medeiros, Sylvie Bay, Christelle Ganneau, Gonzalo Obal, Eduardo Osinaga, Richard Lo-Man, Mariela Bollati-Fogolín, Nora Berois, Edith Dériaud, Daniel Mazal
Přispěvatelé: Departamento de Anatomia Patologica y Citologia del Hospital de la Mujer, Centro Hospitalario Pereira Rossell, Régulation Immunitaire et Vaccinologie, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie Organique, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Chimie des Biomolécules - Chemistry of Biomolecules, Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), Departamento de Inmunobiologia, Facultad de Medicina, Universidad de la República [Montevideo] (UDELAR), Departamento de Bioquímica, Facultad de Medicina, Departamento de inmunobiologia, Facultad de Medicina- Universidad de la República [Montevideo] (UDELAR), Tumor Immunology and Glycobiology / Glicobiología e Inmunobiología Tumoral [Montevideo], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), This work was supported by grants from Programmes Transversaux de Recherche (PTR, Institut Pasteur, Paris, France) and ECOS France-Uruguay Program to Eduardo Osinaga, Sylvie Bay and Claude Leclerc and from the Ligue Nationale Contre le Cancer (Equipe Labellisee 2011) and Banque Privee Europeenne to Claude Leclerc, and Programa Grupos de Investigacion (CSIC, Universidad de la Republica, Uruguay) to Eduardo Osinaga and Otto Pritsch., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Universidad de la República [Montevideo] (UCUR), Facultad de Medicina- Universidad de la República [Montevideo] (UCUR)
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Cancer Immunology, Immunotherapy
Cancer Immunology, Immunotherapy, 2013, 62 (6), pp.1107-22. ⟨10.1007/s00262-013-1425-7⟩
Cancer Immunology, Immunotherapy, Springer Verlag, 2013, 62 (6), pp.1107-22. ⟨10.1007/s00262-013-1425-7⟩
ISSN: 0340-7004
1432-0851
Popis: International audience; 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.
Databáze: OpenAIRE
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