MAb 806 Enhances the Efficacy of Ionizing Radiation in Glioma Xenografts Expressing the de2-7 Epidermal Growth Factor Receptor

Journal Article · Fri Oct 01 00:00:00 EDT 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.03.027· OSTI ID:21451158

Johns, Terrance G ^[1]; McKay, Michael J ^[2]; Cvrljevic, Anna N; Gan, Hui K ^[1]; Taylor, Caitlin; Huiling, Xu ^[2]; Smyth, Fiona E ^[3]

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1. Oncogenic Signalling Laboratory, Ludwig Institute for Cancer Research, Heidelberg, Victoria (Australia)
2. DNA Repair Laboratory, Divisions of Radiation Oncology and Research, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia)
3. Tumour Targeting Laboratory, Ludwig Institute for Cancer Research, Heidelberg, Victoria (Australia)

Purpose: Mutations of the epidermal growth factor receptor (EGFR) are common in glioma. The most frequent mutation, de2-7 EGFR/EGFRvIII, occurs in approximately 40% of high-grade gliomas and confers resistance to ionizing radiation (IR). We have previously shown that mAb 806, a novel EGFR-specific antibody, is able to inhibit the growth of U87MG.{Delta}2-7 glioma xenografts expressing the de2-7 EGFR and may have potential as a therapeutic. Methods and Materials: Nude mice bearing U87MG.{Delta}2-7 xenografts were treated with mAb 806 and/or IR. Comparison of tumor volumes, the effect of treatment on angiogenesis as determined by mean vessel density, and expression changes in prosurvival protein pAkt between treatment groups were undertaken. Results: Treatment of mice bearing U87MG.{Delta}2-7 xenografts with mAb 806 and IR resulted in schedule-dependent radiosensitization. Maximal benefit was obtained when antibody treatment was given before irradiation, with the greatest inhibition of both tumor angiogenesis and tumor growth. Combination treatment mediated radiosensitization by selectively blocking the phosphorylation of the prosurvival protein Akt at serine 473, a process that is independent of DNA-dependent protein kinase catalytic subunit. Conclusions: Our results provide a rationale for the use of mAb 806 in combination with IR for the treatment of glioma and potentially other solid tumors bearing the de2-7 EGFR.

• OSTI ID: 21451158
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 78, Issue 2; Other Information: DOI: 10.1016/j.ijrobp.2010.03.027; PII: S0360-3016(10)00504-3; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

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