medigraphic.com
ISSN 1027-2852 (Electronic)
ISSN 0864-4551 (Print)

2017, Number 1

Next >>

Biotecnol Apl 2017; 34 (1)

Nimotuzumab-mediated antibody-dependent cellular cytotoxicity activity on target tumor cell lines depends on the expression level of the epidermal growth factor receptor

Chao L, Pérez D, Sánchez B

Language: English
References: 32
Page: 1201-1205
PDF size: 539.27 Kb.


ABSTRACT

The epidermal growth factor receptor (EGFR) is an attractive target for cancer treatment due to its major role in tumor development. For this reason, the nimotuzumab monoclonal antibody (mAb) was developed. This is a humanized monoclonal antibody specific for the extracellular domain of EGFR that inhibits its signaling cascades and arrest the cell cycle in epithelial tumor cell lines. At the same time, it is known that the antibody dependent cellular cytotoxicity (ADCC) response is one of the critical mechanisms underlying the clinical efficacy of some therapeutic anticancer mAbs. However, there were no reports on the capacity of nimotuzumab to mediate this effect. Therefore, in this work, the ability of nimotuzumab to induce ADCC was investigated, as well as the influence of EGFR expression levels on this mechanism of action. It was demonstrated that this mAb is able to mediate ADCC against cultured cell lines, which increases with an increase in mAb’s concentration and the effect directly depending on the level of EGFR expression. These results suggest ADCC activity as one of the potential therapeutic mechanisms mediating the action of nimotuzumab in patients with high EGFR expression tumors.


REFERENCES

  1. Seshacharyulu P, Ponnusamy MP, Haridas D, Jain M, Ganti AK, Batra SK. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012;16(1):15-31

  2. Yarden Y, Pines G. The ERBB network: at last, cancer therapy meets systems biology. Nat Rev Cancer. 2012;12(8):553-63.

  3. El Guerrab A, Bamdad M, Kwiatkowski F, Bignon YJ, Penault-Llorca F, Aubel C. Anti-EGFR monoclonal antibodies and EGFR tyrosine kinase inhibitors as combination therapy for triple-negative breast cancer. Oncotarget. 2016;7(45):73618-37.

  4. Kawamoto T, Sato JD, Le A, Polikoff J, Sato GH, Mendelsohn J. Growth stimulation of A431 cells by epidermal growth factor: identification of high-affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody. Proc Natl Acad Sci U S A. 1983;80(5):1337-41.

  5. Tyagi P. Recent results and ongoing trials with panitumumab (ABX-EGF), a fully human anti-epidermal growth factor receptor antibody, in metastatic colorectal cancer. Clin Colorectal Cancer. 2005;5(1):21-3.

  6. Mateo C, Moreno E, Amour K, Lombardero J, Harris W, Perez R. Humanization of a mouse monoclonal antibody that blocks the epidermal growth factor receptor: recovery of antagonistic activity. Immunotechnology. 1997;3(1):71-81.

  7. Reddy BK, Lokesh V, Vidyasagar MS, Shenoy K, Babu KG, Shenoy A, et al. Nimotuzumab provides survival benefit to patients with inoperable advanced squamous cell carcinoma of the head and neck: a randomized, open-label, phase IIb, 5-year study in Indian patients. Oral Oncol. 2014;50(5):498-505.

  8. Massimino M, Biassoni V, Miceli R, Schiavello E, Warmuth-Metz M, Modena P, et al. Results of nimotuzumab and vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood. J Neurooncol. 2014;118(2):305-12.

  9. Zhai RP, Ying HM, Kong FF, Du CR, Huang S, Zhou JJ, et al. Experience with combination of nimotuzumab and intensity-modulated radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. Onco Targets Ther. 2015;8:3383-90.

  10. Crombet T, Figueredo J, Salomón Cárdenas M, Selva JC, Toledo C, Vaquer J, et al. Use the humanized anti-EGFR MAb (nimotuzumab) and irradiation for the treatment of high grade glioma patients [abstract]. Eur J Cancer 2008;6(12):168.

  11. Rojo F, Gracias E, Villena N, Cruz T, Corominas JM, Corradino I, et al. Pharmacodynamic trial of nimotuzumab in unresectable squamous cell carcinoma of the head and neck: a SENDO Foundation study. Clin Cancer Res. 2010;16(8):2474-82.

  12. Ramos-Suzarte M, Lorenzo-Luaces P, Lazo NG, Perez ML, Soriano JL, Gonzalez CE, et al. Treatment of malignant, non-resectable, epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy. Cancer Biol Ther. 2012;13(8):600-5.

  13. Crombet-Ramos T, Rak J, Perez R, Viloria-Petit A. Antiproliferative, antiangiogenic and proapoptotic activity of h-R3: A humanized anti-EGFR antibody. Int J Cancer. 2002;101(6):567-75.

  14. Trotta AM, Ottaiano A, Romano C, Nasti G, Nappi A, De Divitiis C, et al. Prospective evaluation of cetuximab-mediated Antibody-Dependent Cell Cytotoxicity in metastatic colorectal cancer patients predicts treatment efficacy. Cancer Immunol Res. 2016;4(4):366-74.

  15. Bibeau F, Lopez-Crapez E, Di Fiore F, Thezenas S, Ychou M, Blanchard F, et al. Impact of Fc{gamma}RIIa-Fc{gamma} RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J Clin Oncol. 2009;27(7):1122-9.

  16. Rodriguez J, Zarate R, Bandres E, Boni V, Hernandez A, Sola JJ, et al. Fc gamma receptor polymorphisms as predictive markers of Cetuximab efficacy in epidermal growth factor receptor downstreammutated metastatic colorectal cancer. Eur J Cancer. 2012;48(12):1774-80.

  17. Bergh J, Nilsson K, Ekman R, Giovanella B. Establishment and characterization of cell lines from human small cell and large cell carcinomas of the lung. Acta Pathol Microbiol Immunol Scand A. 1985;93(3):133-47.

  18. Peipp M, Lammerts van Bueren JJ, Schneider-Merck T, Bleeker WW, Dechant M, Beyer T, et al. Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells. Blood. 2008;112(6):2390-9.

  19. International Conference on Harmonisation Working Group. ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice E6 (R1). International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; 1996 [cited 2016 Mar 24]. Available from: http://www.ich. org/fileadmin/Public_Web_Site/ICH_Products/ Guidelines/Efficacy/ E6_R1/Step4/ E6_R1__Guideline.pdf

  20. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects [Internet]. Ferney-Voltaire: World Medical Association, Inc.; 2016 [cited 2016 Oct 11]. Available from: http://www. wma.net/ en/30publications/10policies/b3/.

  21. Roque-Navarro L, Mateo C, Lombardero J, Mustelier G, Fernandez A, Sosa K, et al. Humanization of predicted T-cell epitopes reduces the immunogenicity of chimeric antibodies: new evidence supporting a simple method. Hybrid Hybridomics. 2003;22(4):245-57.

  22. Haigler H, Ash JF, Singer SJ, Cohen S. Visualization by fluorescence of the binding and internalization of epidermal growth factor in human carcinoma cells A-431. Proc Natl Acad Sci U S A. 1978;75(7):3317-21.

  23. Bates SE, Valverius EM, Ennis BW, Bronzert DA, Sheridan JP, Stampfer MR, et al. Expression of the transforming growth factor-alpha/epidermal growth factor receptor pathway in normal human breast epithelial cells. Endocrinology. 1990;126(1):596-607.

  24. Suarez Pestana E, Greiser U, Sanchez B, Fernandez LE, Lage A, Perez R, et al. Growth inhibition of human lung adenocarcinoma cells by antibodies against epidermal growth factor receptor and by ganglioside GM3: involvement of receptordirected protein tyrosine phosphatase(s). Br J Cancer. 1997;75(2):213-20.

  25. Sherwood ER, Van Dongen JL, Wood CG, Liao S, Kozlowski JM, Lee C. Epidermal growth factor receptor activation in androgen-independent but not androgen-stimulated growth of human prostatic carcinoma cells. Br J Cancer. 1998;77(6):855-61.

  26. Garrido G, Tikhomirov IA, Rabasa A, Yang E, Gracia E, Iznaga N, et al. Bivalent binding by intermediate affinity of nimotuzumab: a contribution to explain antibody clinical profile. Cancer Biol Ther. 2011;11(4):373-82.

  27. Crombet T, Osorio M, Cruz T, Roca C, del Castillo R, Mon R, et al. Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients. J Clin Oncol. 2004;22(9):1646-54.

  28. Talavera A, Friemann R, Gomez-Puerta S, Martinez-Fleites C, Garrido G, Rabasa A, et al. Nimotuzumab, an antitumor antibody that targets the epidermal growth factor receptor, blocks ligand binding while permitting the active receptor conformation. Cancer Res. 2009;69(14):5851-9.

  29. Akashi Y, Okamoto I, Iwasa T, Yoshida T, Suzuki M, Hatashita E, et al. Enhancement of the antitumor activity of ionising radiation by nimotuzumab, a humanised monoclonal antibody to the epidermal growth factor receptor, in non-small cell lung cancer cell lines of differing epidermal growth factor receptor status. Br J Cancer. 2008;98(4):749-55.

  30. Basavaraj C, Sierra P, Shivu J, Melarkode R, Montero E, Nair P. Nimotuzumab with chemoradiation confers a survival advantage in treatment-naive head and neck tumors over expressing EGFR. Cancer Biol Ther. 2010;10(7):673-81.

  31. Derer S, Bauer P, Lohse S, Scheel AH, Berger S, Kellner C, et al. Impact of epidermal growth factor receptor (EGFR) cell surface expression levels on effector mechanisms of Received in October, 2016. Accepted in March, 2017. EGFR antibodies. J Immunol. 2012;189(11): 5230-9.

  32. Srivastava RM, Lee SC, Andrade Filho PA, Lord CA, Jie HB, Davidson HC, et al. Cetuximab- activated natural killer and dendritic cells collaborate to trigger tumor antigenspecific T-cell immunity in head and neck cancer patients. Clin Cancer Res. 2013;19(7): 1858-72.




2020     |     www.medigraphic.com