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Molecular Cloning of a Monoclonal Anti-Tumor Antibody Specific for the Tn Antigen and Expression of an Active Single-Chain Fv Fragment

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Babino, Alvaro | Pritsch, Otto | Oppezzo, Pablo | Du Pasquier, Renaud | Roseto, Alberto | Osinaga, Eduardo | Alzari, Pedro, M.

Edité par CCSD ; Mary Ann Liebert -

International audience. We report here the first amino acid sequence of an anti-Tn monoclonal antibody raised against human breast cancer cells and show that a single chain Fv fragment of this IgM retains the Tn-binding specificity as defined by functional assays with asialo-OSM and membrane extracts from MCF-7 cells. Sequence comparisons and molecular modeling of 83D4 indicate that the antibody combining site displays a cavity-like feature primarily defined by the CDR H1 and H2 loops. This pocket could accommodate a single Tn molecule, thus, suggesting a structural explanation for the predominant expression of a particular VH gene segment in a group of antibodies that recognize tumor-associated antigens arising from an aberrant O-glycosylation.

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