Novel antigenic specificity involving the blood group antigen, Lea, in combination with onco-developmental antigen, SSEA-1, recognized by two monoclonal antibodies to human milk-fat globule membranes

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Abstract

Two monoclonal antibodies to human milk-fat globule membranes, which recognize an epithelial antigen designated MAM-3c, were found to bind strongly to epithelial glycoproteins derived from non-secretors. Further investigations, using purified glycoproteins and structurally defined ollgosaccharides, established that the optimal antigenic structure for both antibodies involves the Type 1 based blood group antigen. Lea. In combination with the Type 2 based onco-developmental antigen. SSEA-1.

as in lacto-N-difucohexaose II. The antibodies may also react with the corresponding monofucosyl structures lacking the 3- or 4- linked fucose residues and to a lesser extent with the afucosyl tetrasaccharide sequence as in lacto-N-tetraose. The Lea and SSEA-1 antigens are known to occur on human epithelial glycoproteins. However, this is the first report of an antigenic specificity involving a combination of the Type 1 and Type 2 based fuco-oligosaccharides and occurring on epithelial glycoproteins.

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      The LeaLex TACA also displays epitopes selectively recognized by two other mAbs, 115C2 and 11SG3, raised against human milk-fat globule membranes.8 Since these mAbs were also shown to react weakly with the non-fucosylated lacto-N-tetraose (LNT) backbone (Table 1), it was suggested that they recognize an internal epitope within the LeaLex structures.8 As a cell surface epitope specific to cancer cells and a prognostic marker for carcinomas,2–4,6,9–11 the epitope recognized by mAb 43-9F is of great interest to develop LeaLex-based cancer immunotherapeutics.

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    HCG is supported by the Leukaemia Research Fund of Great Britain.

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