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Epitope-specific Antibody Response to HT-1080 Fibrosarcoma Cells by Mimotope Immunization¹

Institut National Recherche Scientifique, Institute Armand-Frappier, University of Quebec, Laval, Quebec, H7V 1B7 Canada [M. P., S. S-G., V. A.]; Supratek Pharma Inc., Laval, Quebec, H7V 1B7 Canada [V. A.]; Department of Biological Sciences, University of Quebec in Montreal, Montreal, Quebec, H3C 3P8 Canada [R. M.]; and Biophage Inc., 6100 Royalmount Avenue, Montreal, Quebec, H4P 2R2 Canada [R. M.]

Mouse monoclonal antibody (mAb) BCD-F9, which recognizes an unknown antigen found on the surface of many tumor cells, was used to screen a phage display library expressing random peptide decamers. The phage that was selected encoded the unique sequence GRRPGGWWMR, representing the peptide capable of binding to the BCD-F9 mAb. The peptide was synthesized and found to specifically inhibit the binding of mAb to HT-1080 fibrosarcoma cells. Alanine mutagenesis of the sequence encoding this peptide indicated that three residues, PXXWW, were critical for its binding to the BCD-F9 mAb. Polyclonal antibodies generated by immunization of rabbits with the synthetic peptide GRRPGGWWMR (anti-mimotope antiserum or AM-F9) bound specifically to HT-1080 cells and inhibited the binding of the BCD-F9 mAb to these cells. Using an experimental animal model in which CD-1 nude mice are inoculated i.v. with HT-1080 cells, develop lung metastasis, and die within 30 days, we have shown that AM-F9 could significantly prolong the life span of these animals. Our results suggest that a peptide mimotope can potentially be used as a novel immunotherapy to induce a beneficial antitumor response.

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