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

• Published in: Clinical cancer research Vol. 6; no. 9; pp. 3629 - 3635
• Main Authors: Popkov, M, Sidrac-Ghali, S, Alakhov, V, Mandeville, R
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-09-2000
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - metabolism; Antibodies, Neoplasm - biosynthesis; Antibodies, Neoplasm - immunology; Antibodies, Neoplasm - metabolism; Antibody Specificity - immunology; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Antineoplastic agents; Binding Sites, Antibody; Biological and medical sciences; Epitopes - immunology; Female; Fibrosarcoma - immunology; Fibrosarcoma - secondary; Fibrosarcoma - therapy; Humans; Immunization, Passive; Immunotherapy; Lung Neoplasms - immunology; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Mimicry - immunology; Molecular Sequence Data; Oligopeptides - immunology; Oligopeptides - pharmacology; Peptide Library; Pharmacology. Drug treatments; Rabbits; Tumor Cells, Cultured; Antineoplastic agent; Antigenic determinant; Peptides; Rabbit; Fibrosarcoma; Monoclonal antibody; Metastasis; Mimetism; Bronchopulmonary; Specificity; Immunotherapy; Established cell line; Tumor cell; Human; Lung disease; Immunization; Sarcoma; Respiratory disease; Rodentia; Malignant tumor; Lagomorpha; In vitro; In vivo; Vertebrata; Mammalia; Synthetic product; Treatment; Mouse; Animal
• ISSN: 1078-0432; 1557-3265

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,
P XX WW, 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.