title: The Quest for Anticancer Vaccines: Deciphering the Fine-Epitope Specificity of Cancer-Related Monoclonal Antibodies by Combining Microarray Screening and Saturation Transfer Difference NMR.
abstract: The identification of MUC1 tumor-associated Tn antigen (αGalpNAc1-O-Ser/Thr) has boosted the development of anticancer vaccines. Combining microarrays and saturation transfer difference NMR, we have characterized the fine-epitope mapping of a MUC1 chemical library (naked and Tn-glycosylated) toward two families of cancer-related monoclonal antibodies (anti-MUC1 and anti-Tn mAbs). Anti-MUC1 mAbs clone VU-3C6 and VU-11E2 recognize naked MUC1-derived peptides and bind GalNAc in a peptide-sequence-dependent manner. In contrast, anti-Tn mAbs clone 8D4 and 14D6 mostly recognize the GalNAc and do not bind naked MUC1-derived peptides. These anti-Tn mAbs show a clear preference for glycopeptides containing the Tn-Ser antigen rather than the Tn-Thr analogue, stressing the role of the underlying amino acid (serine or threonine) in the binding process. The reported strategy can be employed, in general, to unveil the key minimal structural features that modulate antigen-antibody recognition, with particular relevance for the development of Tn-MUC1-based anticancer vaccines.
authors.affiliation: UCIBIO, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa , 2829-516 Caparica, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Coelho
authors.affiliation: Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University , Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University , Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Gerard
authors.initials: G
authors.lastname: Artigas
authors.affiliation: Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University , Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hinou
authors.affiliation: Centro de Investigaciones Biológicas, CIB-CSIC , 28040 Madrid, Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Cañada
authors.affiliation: Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, Institut Pasteur , 75724 Paris Cedex 15, France.|INSERM U1041 , 75724 Paris Cedex 15, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Lo-Man
authors.affiliation: Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, Institut Pasteur , 75724 Paris Cedex 15, France.|INSERM U1041 , 75724 Paris Cedex 15, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
authors.affiliation: UCIBIO, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa , 2829-516 Caparica, Portugal.
authors.forename: Eurico J
authors.initials: EJ
authors.lastname: Cabrita
authors.affiliation: CIC bioGUNE Bizkaia , 48160 Derio, Spain.|Ikerbasque, Basque Foundation for Science , 48005 Bilbao, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.affiliation: Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University , Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Nishimura
authors.affiliation: Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University , Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Fayna
authors.initials: F
authors.lastname: Garcia-Martín
authors.affiliation: UCIBIO, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa , 2829-516 Caparica, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Marcelo
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism*; D019496:Cancer Vaccines; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D040081:Protein Array Analysis
chemical_list: D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D000939:Epitopes