Anti-epidermal growth factor receptor monoclonal antibody cetuximab augments radiation effects in glioblastoma multiforme in vitro and in vivo
Anti-epidermal growth factor receptor monoclonal antibody cetuximab augments radiation effects in glioblastoma multiforme in vitro and in vivo
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DOI：
10.1227/01.neu.0000145865.25689.55
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发表时间：
2005-01-01
期刊：
影响因子：
4.8
通讯作者：
Canute, GW
中科院分区：
文献类型：
--
作者：
Eller, JL;Longo, SL;Canute, GW
目的：以前，我们证明了抗表皮生长因子受体（EGFR）抗体西妥昔单抗单独在体内和体外对EGFR扩增的多形性胶质母细胞瘤（GBM）细胞有效。本工作的目的是进一步研究西妥昔单抗作为单一疗法的有效性，以及将其与放射治疗或chemotherapy.METHODS相结合：EGFR扩增的GBM细胞被植入无论是在裸小鼠的侧翼，以确定西妥昔单抗对较大的肿瘤负荷或颅内的有效性，以评估西妥昔单抗的能力，通过血脑屏障。细胞也暴露于西妥昔单抗结合放射线在体内或化疗药物在vitro.RESULTS：增加肿瘤负荷在小鼠的侧腹肿瘤生长抑制量下降。对于使用西妥昔单抗5周的前两个颅内模型，与对照组相比，治疗组小鼠的中位生存期显著增加。当无限期给予西妥昔单抗时，结果是令人鼓舞的，治疗组的中位生存期增加尚未达到但至少900%。侧腹GBM暴露于西妥昔单抗和放射的小鼠的中位生存期比单独使用任一种治疗的小鼠的中位生存期增加更大。初步在体外实验中使用西妥昔单抗和化疗药物表现出增加cytotoxic.CONCLUSION：这些结果是令人鼓舞的，证明西妥昔单抗对EGFR扩增GBM的有效性。令人惊讶的是，西妥昔单抗在颅内模型中全身给药时有效。辐射增强了西妥昔单抗在体外和体内对GBM的作用。体外分析也证明了化疗药物的累加效应。这些结果证实了西妥昔单抗的EGFR阻断作为针对人GBM的潜在治疗。
OBJECTIVE: Previously, we demonstrated that the anti-epidermal growth factor receptor (EGFR) antibody cetuximab alone was effective against EGFR-amplified glioblastoma multiforme (GBM) cells in vivo and in vitro. The purpose of the present work was to study further the effectiveness of cetuximab as a monotherapy as well as combining it with radiation therapy or chemotherapy.METHODS: EGFR-amplified GBM cells were implanted either in the flanks of nude mice to determine the effectiveness of cetuximab on larger tumor burden or intracranially to assess the ability of cetuximab to cross the blood-brain barrier. Cells were also exposed to cetuximab in combination with radiation in vivo or chemotherapeutic agents in vitro.RESULTS: Increasing tumor burden in the flanks of mice decreased the amount of tumor growth inhibition. For the first two intracranial models using cetuximab for 5 weeks, the treated mice had a significant increase in median survival compared with controls. When cetuximab was given indefinitely, the results were encouraging, with an increase in median survival for the treated group not yet reached but at least 900%. Mice with flank GBM exposed to cetuximab and radiation had a larger increase in median survival than those with either treatment alone. Preliminary in vitro experiments using cetuximab and chemotherapeutic agents showed increased cytotoxicity.CONCLUSION: These results were encouraging, demonstrating the effectiveness of cetuximab against EGFR-amplified GBM. Surprisingly, cetuximab was effective when administered systemically in an intracranial model. Radiation augmented the effect of cetuximab on GBM in vitro and in vivo. In vitro analysis demonstrated additive effects for chemotherapeutic agents as well. These results confirm EGFR blockade with cetuximab as a potential treatment against human GBM.