Epitope-specific antibody response to HT-1080 fibrosarcoma cells by mimotope immunization.
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.
Popkov
M
M
Institut National Recherche Scientifique, Institute Armand-Frappier, University of Quebec, Laval, Canada.
Sidrac-Ghali
S
S
Alakhov
V
V
Mandeville
R
R
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D006801:Humans; D007116:Immunization, Passive; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018716:Molecular Mimicry / Q000276:immunology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology* / Q000494:pharmacology; D019151:Peptide Library; D011817:Rabbits; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000939:Epitopes; D009842:Oligopeptides; D019151:Peptide Library