Immunization with Mimotopes Prevents Growth of Carcinoembryonic Antigen–Positive Tumors in BALB/c Mice

作者: Kira H. Brämswig , Regina Knittelfelder , Silke Gruber , Eva Untersmayr , Angelika B. Riemer

DOI: 10.1158/1078-0432.CCR-07-0692

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摘要: Purpose: The carcinoembryonic antigen (CEA) is a glycoprotein that overexpressed in nearly 50% of all human and veterinarian tumors. At present, anti-CEA antibodies are being tested clinical studies as passive immunotherapeutics. This study aims to establish an active immunotherapy for the poorly immunogenic CEA by generating surrogates. Experimental Design: We used monoclonal antibody Col-1 biopanning method generate peptide mimics (mimotopes) epitope. showing highest specificity mimicry was synthesized octameric multiple antigenic mimotope (MAM). Subsequently, immunogenicity selected examined BALB/c mice. assessed antibody-dependent cellular cytotoxicity complement-dependent mediated induced on CEA-expressing HT29 tumor cells. Furthermore, after immunization, mice were transplanted s.c. with Meth-A/CEA Results: When immunized this MAM, they generated specific humoral immune response against CEA. mimotope-induced polyclonal poly-isotypic vitro . when MAM-immunized cells expressing CEA, suppressed growth observed. Conclusion: From our results, we can conclude epitope be translated into mimic. recognize do effectively inhibit CEA-positive Based these finding, suggest mimotopes candidates

参考文章(34)
Luca Mazzucchelli, James B. Burritt, Algirdas J. Jesaitis, Asma Nusrat, Tony W. Liang, Andrew T. Gewirtz, Frederick J. Schnell, Charles A. Parkos, Cell-specific peptide binding by human neutrophils. Blood. ,vol. 93, pp. 1738- 1748 ,(1999) , 10.1182/BLOOD.V93.5.1738
G. H. Sato, J. Mendelsohn, J. Polikoff, J. D. Sato, A. D. Le, T. Kawamoto, Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. Molecular biology & medicine. ,vol. 1, pp. 511- 529 ,(1983)
Thomas Kieber-Emmons, Ping Luo, Jianping Qiu, Tylis Y. Chang, Insug O, Magdalena Blaszczyk-Thurin, Zenon Steplewski, Vaccination with carbohydrate peptide mimotopes promotes anti-tumor responses Nature Biotechnology. ,vol. 17, pp. 660- 665 ,(1999) , 10.1038/10870
Angelika B. Riemer, Markus Klinger, Stefan Wagner, Astrid Bernhaus, Luca Mazzucchelli, Hubert Pehamberger, Otto Scheiner, Christoph C. Zielinski, Erika Jensen-Jarolim, Generation of Peptide mimics of the epitope recognized by trastuzumab on the oncogenic protein Her-2/neu. Journal of Immunology. ,vol. 173, pp. 394- 401 ,(2004) , 10.4049/JIMMUNOL.173.1.394
Robert Kammerer, Detlef Stober, Petra Riedl, Claude Oehninger, Reinhold Schirmbeck, Jörg Reimann, Noncovalent association with stress protein facilitates cross-priming of CD8+ T cells to tumor cell antigens by dendritic cells. Journal of Immunology. ,vol. 168, pp. 108- 117 ,(2002) , 10.4049/JIMMUNOL.168.1.108
P. Noguchi, D. Wunderlich, R. Muraro, A. Thor, R. Cunningham, J. Schlom, J. Lundy, Definition by Monoclonal Antibodies of a Repertoire of Epitopes on Carcinoembryonic Antigen Differentially Expressed in Human Colon Carcinomas versus Normal Adult Tissues Cancer Research. ,vol. 45, pp. 5769- 5780 ,(1985)
R. Handgretinger, K. Anderson, P. Lang, R. Dopfer, T. Klingebiel, M. Schrappe, P. Reuland, S.D. Gillies, R.A. Reisfeld, D. Niethammer, A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma European Journal of Cancer. ,vol. 31, pp. 261- 267 ,(1995) , 10.1016/0959-8049(94)00413-Y
Stephen D. Gillies, Kin-Ming Lo, John Wesolowski, High-level expression of chimeric antibodies using adapted cDNA variable region cassettes Journal of Immunological Methods. ,vol. 125, pp. 191- 202 ,(1989) , 10.1016/0022-1759(89)90093-8
Christophe Boeckler, Dominique Dautel, Philippe Schelté, Benoît Frisch, Dominique Wachsmann, Jean-Paul Klein, Francis Schuber, Design of highly immunogenic liposomal constructs combining structurally independent B cell and T helper cell peptide epitopes. European Journal of Immunology. ,vol. 29, pp. 2297- 2308 ,(1999) , 10.1002/(SICI)1521-4141(199907)29:07<2297::AID-IMMU2297>3.0.CO;2-5