EFFICACY EVALUATION OF A MONOCLONAL ANTIBODY AGAINST THE EPIDERMAL GROWTH FACTORS RECEPTOR IN THE MODEL OF SUBCUTANEOUS XENOGRAFT IN IMMUNODEFICIENT MICE
Abstract
This article presents the results of the comparative antitumor efficacy study of two test articles of therapeutic humanized monoclonal antibodies against epidermal growth factor receptor (EGFR) manufactured by Russian biopharmaceutical company CJSC “Biocad” and the commercial drug “Erbitux®” (Merck, Germany) in subcutaneous xenografts model using human epidermoid carcinoma A431NS cell line. EGFR overexpression in epithelial tumor cells is a commonly known fact that determines use of this receptor as a target for therapeutic monoclonal antibodies. The basic mechanism of action of such drugs is blocking of epithelial cells proliferation through competitive binding to EGFR. Evaluation of tumor growth dynamics in immunodeficient (Nu/Nu) mice was performed during in vivo experiment using two parameters: tumor growth index and tumor growth inhibition (TGI, %). The results received with used study design show that antitumor effects of the test articles manufactured by CJSC “Biocad” and the commercial comparator drug “Erbitux®” estimated by values of TGI and tumor growth index are comparable.
About the Authors
Ya. Yu. Ustyugov
Biocad JSC, Moscow Region, Lyubuchany
Russian Federation
Russian Federation
Ustyugov Yakov Yurevich, PhD, Head of Experimental Biology Laboratory.
Phone: +7 (495) 992-66-28. E-mail: ustjugov@biocad.ru
A. A. Aleksandrov
Biocad JSC, Moscow Region, Lyubuchany
Russian Federation
Russian Federation
Alexandrov Alexey Alexandrovich, researcher, Experimental Biology Laboratory.
Phone: +7 (495) 992-66-28. E-mail: aleksandrov@biocad.ru
M. V. Artyukova
Biocad JSC, Moscow Region, Lyubuchany
Russian Federation
Russian Federation
Artyukhova Marina Vladimirovna, researcher, Experimental Biology Laboratory.
Phone: +7 (495) 992-66-28. E-mail: artyukhova@biocad.ru
M. A. Varavko
Biocad JSC, Moscow Region, Lyubuchany
Russian Federation
Russian Federation
Varavko Maria Alexandrovna, researcher, Department of preclinical trials of drugs.
Phone: +7 (495) 992-66-28. E-mail: varavko@biocad.ru
References
1. Belenkiy M.L. Elements of quantitative assessment of pharmacological effect. L., 1963. P. 81–117. [in Russian]
2. Daiichi Sankyo Announces Discontinuation of Phase 3 Clinical Trial in Japan of Nimotuzumab (DE-766) in Lung Cancer. URL: http://www.daiichisankyo.com/media_investors/media_relations/press_releases/detail/006115.html (05.03.2015).
3. Freeman D.J., McDorman K., Ogbagabriel S., Kozlosky C., Yang B.B., Doshi S., Perez-Ruxio J.J., Fanslow W., Starnes C., Radinsky R. Tumor penetration and epidermal growth factor receptor saturation by panitumumab correlate with antitumor activity in a preclinical model of human cancer // Mol. Cancer. 2012. Vol. 11. P. 47. d doi: 10.1186/1476- 4598-11-47.
4. Friedman L.M., Rinon A., Schechter B., Lyass L., Lavi S., Bacus S.S., Sela M., Yarden Y. Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: implications for cancer immunotherapy // Proc. Natl. Acad. Sci. USA. 2005. Vol. 102 (6). P. 1915–1920.
5. Kurai J., Chikumi H., Hashimoto K., Yamaguchi K., Yamasaki A., Sako T., Touge H., Makino H., Takata M., Miyata M., Nakamoto M., Burioka N., Shimizu E. Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines // Clin. Cancer Res. 2007. Vol. 13 (5). P. 1552–1561.
6. Lammerts van Bueren J.J., Bleeker W.K., Brännström A., von Euler A., Jansson M., Peipp M., Schneider-Merck T., Valerius T., van de Winkel J.G., Parren P.W. The antibody zalutumumab inhibits epidermal growth factor receptor signaling by limiting intra- and intermolecular flexibility // Proc. Natl. Acad. Sci. USA. 2008. Vol. 105 (16). P. 6109–6114. doi: 10.1073/pnas.0709477105.
7. Li S., Schmitz K.R., Jeffrey P.D., Wiltzius J.J., Kussie P., Ferguson K.M. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab // Cancer Cell. 2005. Vol. 7 (4). P. 301–311.
8. Mendelsohn J., Baselga J. Epidermal growth factor receptor targeting in cancer // Semin. Oncol. 2006. Vol. 33 (4). P. 369–385.
9. Nicholson R.I., Gee J.M., Harper M.E. EGFR and cancer prognosis // Eur. J. Cancer. 2001. Vol. 37. Suppl 4. P. 9–15.
10. Pedersen M.W., Jacobsen H.J., Koefoed K., Hey A., Pyke C., Haurum J.S., Kragh M. A Novel Synergistic Anti–Epidermal Growth Factor Receptor Antibody Mixture with Superior Anticancer Efficacy // Cancer Res. 2010. Vol. 70 (2). P. 588–597. doi: 10.1158/0008-5472.CAN-09-1417.
11. Pharmacology / toxicology review and evaluation. URL: http:// www.accessdata.fda.gov/drugsatfda_docs/bla/2004/125084_ERBITUX_PHARMR_P1.PDF (05.03.2015).
12. Rogers J.E., Eng C. Cetuximab in Refractory Squamous Cell Carcinoma of the Anal Canal // J Gastrointest Cancer. 2014. Vol. 45. Suppl. 1. P. 198–200. doi: 10.1007/s12029-014-9626-7.
13. Scientific discussion. URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000558/WC500029113.pdf (05.03.2015).
14. Sorkin A., Krolenko S., Kudrjavtceva N., Lazebnik J., Teslenko L., Soderquist A.M., Nikolsky N. Recycling of epidermal growth factor-receptor complexes in A431 cells: identification of dual pathways // J. Cell Biol. 1991. Vol. 112 (1). P. 55–63.
15. Travis W.D., Brambilla E., Muller-Hermelink K.H., Harris C.C. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart // World Health Organization Classification of Tumours. Lyon: IARC Press, 2004. 344 p.
Review
For citations:
Ustyugov Ya.Yu., Aleksandrov A.A., Artyukova M.V., Varavko M.A. EFFICACY EVALUATION OF A MONOCLONAL ANTIBODY AGAINST THE EPIDERMAL GROWTH FACTORS RECEPTOR IN THE MODEL OF SUBCUTANEOUS XENOGRAFT IN IMMUNODEFICIENT MICE. Siberian journal of oncology. 2015;1(4):51-57. (In Russ.)
Views:
961
Email this article 
