TITLE:
Preclinical Efficacy of Nimotuzumab, an Anti-Egfr Monoclonal Antibody as a Single Agent Therapy in Human GBM u87mg Xenografts
AUTHORS:
Arlhee Diaz, Rances Blanco, Margit Lemm, Iduna Fichtner, Kalet Leon, Enrique Montero
KEYWORDS:
CD133; Epidermal Growth Factor Receptor; Glioblastoma Multiforme; Nimotuzumab; Radiation;Temozolomide
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.3 No.4,
August
9,
2012
ABSTRACT: Background: The poor prognosis of patients with high-grade glioma multiform (GBM) has led investigators to the search of new therapeutic strategies. Current treatment includes surgery when possible, radiotherapy and chemotherapy. Molecular-targeted therapies are in the process of clinical testing, and promising agents include monoclonal antibodies. Our study examined the antitumor activity of three different single therapies in nude mice bearing both subcutaneous and orthotopic brain xenografts of the U87MG human GBM cell line. Methods: Cell culture, Histology, Immunohistochemistry, Animal experiments, Statistical analysis. Results: Different groups of treatment included nimotuzumab, a humanized monoclonal antibody that inhibits the EGFR tyrosine kinase activity, or total body irradiation, or the chemotherapeutic agent temozolomide (TMZ). For the control group animals received saline solution instead of the antibody. For the subcutaneous model, only nimotuzumab or TMZ produced a significant delay in tumor growth. In the intracranial model, unlike TMZ, the systemic administration of the antibody did not reduce the tumor growth, despite both therapies inhibited the formation of microsatellites in the brain of mice. The antitumor activity of nimotuzumab was accompanied by a decrease in the microvessel density and the proliferative activity of tumor cells. TMZ only inhibited the tumor cell proliferation but not the formation of new tumor-associated microvessels in xenografts. For radiation therapy, neither antiproliferative nor antiangiogenic activity was found, in accordance with the lack of antitumor activity. Only nimotuzumab reduced the frequency of chemo and radioresistant CD133+ population. Conclusion: Our results illustrate the potential efficacy of nimotuzumab as a single agent against an EGFR-amplified human GBM, a tumor resistant to the therapy with all well-known forms of treatment.