Abstract | BACKGROUND: METHODS: We used the phage display technique to identify four peptides structurally mimicking the cetuximab epitope. We coupled two of these peptides to an immunogenic carrier protein, and we vaccinated four groups (n = 8) of BALB/c mice intraperitoneally with 10 microg of the mimotope conjugates, a control peptide conjugate, or the carrier protein alone. We assessed antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity mediated by the induced antibodies against EGFR-overexpressing human A431 carcinoma cells. We then tested receptor internalization capacity of the induced antibodies with fluorescently labeled EGFR, and we assayed their growth inhibitory potential toward A431 cells with a [3H] thymidine proliferation assay. RESULTS: Mimotope-induced antibodies recognized EGFR, and both types of antibody-mediated cytotoxic effects were elicited by these antibodies. In both cellular cytotoxicity assays, the mimotope-induced antibodies exhibited specific lysis of more than 50%. The induced antibodies caused internalization of the receptor from the cell surface into endocytic vesicles and inhibited growth of EGFR-expressing cells to a similar extent as cetuximab [67% (95% confidence interval {CI} = 55% to 79%) and 69% (95% CI = 55% to 84%), respectively]. CONCLUSIONS:
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Authors | Angelika B Riemer, Harald Kurz, Markus Klinger, Otto Scheiner, Christoph C Zielinski, Erika Jensen-Jarolim |
Journal | Journal of the National Cancer Institute
(J Natl Cancer Inst)
Vol. 97
Issue 22
Pg. 1663-70
(Nov 16 2005)
ISSN: 1460-2105 [Electronic] United States |
PMID | 16288119
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Blocking
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- Cancer Vaccines
- DNA, Neoplasm
- Epitopes
- ErbB Receptors
- Cetuximab
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Topics |
- Animals
- Antibodies, Blocking
- Antibodies, Monoclonal
(pharmacology)
- Antibodies, Monoclonal, Humanized
- Antibody-Dependent Cell Cytotoxicity
- Antineoplastic Agents
(pharmacology)
- Bacteriophages
- Binding Sites, Antibody
- Blotting, Western
- Breast Neoplasms
(drug therapy, immunology)
- Cancer Vaccines
(pharmacology)
- Carcinoma, Squamous Cell
(drug therapy, immunology)
- Cell Line, Tumor
- Cetuximab
- DNA, Neoplasm
(analysis)
- Enzyme-Linked Immunosorbent Assay
- Epitopes
- ErbB Receptors
(antagonists & inhibitors)
- Female
- Humans
- Immunization, Passive
(methods)
- Mice
- Mice, Inbred BALB C
- Microscopy, Fluorescence
- Research Design
- Sequence Analysis, DNA
- Signal Transduction
(drug effects)
- Transfection
- Tumor Stem Cell Assay
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