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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Biodistribution and radioimmunotherapy of SCCHN in xenotransplantated SCID mice with a 131I-labelled anti-EpCAM monoclonal antibody.
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Biodistribution and radioimmunotherapy of SCCHN in xenotransplantated SCID mice with a 131I-labelled anti-EpCAM monoclonal antibody.

机译:用131I标记的抗EpCAM单克隆抗体在异种移植SCID小鼠中SCCHN的生物分布和放射免疫疗法。

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BACKGROUND: The mortality from squamous cell carcinoma of the head and neck (SCCHN) remains high and almost unchanged throughout the last decades. Therefore, new therapeutic strategies are urgently needed. One promising approach is the application of radio-labeled antibodies directed against tumor-associated antigens. EpCAM is a transmembrane protein, which is overexpressed on almost all SCCHN, making it a suitable anchor molecule for targeted radioimmunotherapy (RIT). The aim of this study was to establish an animal model to investigate the biodistribution and the therapeutic effect of a radio-labeled EpCAM-specific monoclonal antibody (mAb). MATERIALS AND METHODS: The mAb C215 was labeled with 131I and tested for its antitumor effect against established SCCHN xenografts in SCID mice. Initially, the biodistribution of the mAb in the tumor and different organs was determined with a gamma counter and was calculated as % injected dose/gram tissue. For therapeutic approaches 5, 15 or 25 MBq 131I-labeled mAb was injected as a single bolus into tumor-bearing mice. Control animals received either sodium chloride or the unlabeled mAb. The tumor growth and body weight of the animals were measured at various times after administration of the antibody. RESULTS: Initially, high activity was seen in all organs after systemic administration of 13I-C215. Over time general activity decreased whereas an accumulation of activity was seen in the tumor. Tumor growth was delayed in the groups receiving either 15 MBq or 25 MBq 131I-C215 relative to control groups and the 5 MBq group. However, animals in the high-dose groups suffered from treatment-related toxicity, which led to body weight loss of more than 20%. CONCLUSION: Our data demonstrate that the EpCAM-specific radio-labeled mAb C215 is a promising tool to target SCCHN leading to significant tumor control. Further studies are necessary to increase efficacy and reduce toxicity of this new therapeutic approach.
机译:背景:过去几十年来,头颈部鳞状细胞癌(SCCHN)的死亡率仍然很高,几乎没有变化。因此,迫切需要新的治疗策略。一种有前途的方法是应用针对肿瘤相关抗原的放射性标记抗体。 EpCAM是一种跨膜蛋白,几乎在所有SCCHN中都过表达,使其成为靶向放射免疫疗法(RIT)的合适锚定分子。这项研究的目的是建立一个动物模型,以研究放射性标记的EpCAM特异性单克隆抗体(mAb)的生物分布和治疗效果。材料与方法:用131I标记mAb C215,并测试其对SCID小鼠中已建立的SCCHN异种移植物的抗肿瘤作用。最初,用伽玛计数器确定mAb在肿瘤和不同器官中的生物分布,并计算为注射剂量%/克组织。对于治疗方法,将5、15或25 MBq 131I标记的mAb作为单次推注注射到荷瘤小鼠中。对照动物接受氯化钠或未标记的mAb。在施用抗体后的不同时间测量动物的肿瘤生长和体重。结果:最初,全身性施用13I-C215后在所有器官中均观察到高活性。随着时间的流逝,一般活性降低,而在肿瘤中发现活性积累。相对于对照组和5 MBq组,接受15 MBq或25 MBq 131I-C215的组中的肿瘤生长被延迟。但是,高剂量组的动物遭受与治疗有关的毒性,导致体重减轻超过20%。结论:我们的数据表明,EpCAM特异性放射性标记的mAb C215是靶向SCCHN并有望显着控制肿瘤的有前途的工具。为了提高疗效并降低这种新治疗方法的毒性,需要进行进一步的研究。

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