Andratschke Michaela, Gildehaus Franz Josef, Johannson Veronika, Schmitt Baerbel, Mack Brigitte, Reisbach Gilbert, Lang Stephan, Lindhofer Horst, Zeidler Reinhard, Wollenberg Barbara, Luebbers Christian W
Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-University of Munich, Germany.
Anticancer Res. 2007 Jan-Feb;27(1A):431-6.
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).
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.
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%.
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.
头颈部鳞状细胞癌（SCCHN）的死亡率在过去几十年中一直居高不下且几乎没有变化。因此，迫切需要新的治疗策略。一种有前景的方法是应用针对肿瘤相关抗原的放射性标记抗体。上皮细胞黏附分子（EpCAM）是一种跨膜蛋白，在几乎所有头颈部鳞状细胞癌中均过度表达，使其成为靶向放射免疫治疗（RIT）的合适锚定分子。本研究的目的是建立一种动物模型，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。
单克隆抗体C215用131I标记，并测试其对SCID小鼠中已建立的头颈部鳞状细胞癌异种移植瘤的抗肿瘤作用。最初，用γ计数器测定单克隆抗体在肿瘤和不同器官中的生物分布，并计算为每克组织注射剂量的百分比。对于治疗方法，将5、15或25 MBq的131I标记单克隆抗体作为单次推注注入荷瘤小鼠体内。对照动物接受氯化钠或未标记的单克隆抗体。在给予抗体后的不同时间测量动物的肿瘤生长和体重。
最初，全身给予131I-C215后，所有器官均出现高活性。随着时间的推移，总体活性下降，而肿瘤中出现活性积累。相对于对照组和5 MBq组，接受15 MBq或25 MBq 131I-C215的组中肿瘤生长延迟。然而，高剂量组的动物出现与治疗相关的毒性，导致体重减轻超过20%。
我们的数据表明，EpCAM特异性放射性标记单克隆抗体C215是一种有前景的靶向头颈部鳞状细胞癌的工具，可导致显著的肿瘤控制。需要进一步研究以提高这种新治疗方法的疗效并降低其毒性。
