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用于免疫闪烁显像研究的人源化与鼠源抗人表皮生长因子受体单克隆抗体

Humanized versus murine anti-human epidermal growth factor receptor monoclonal antibodies for immunoscintigraphic studies.

作者信息

Morales A A, Ducongé J, Alvarez-Ruiz D, Becquer-Viart M L, Núñez-Gandolff G, Fernández E, Caballero-Torres I, Iznaga-Escobar N

机构信息

Center of Molecular Immunology, Havana, Cuba.

出版信息

Nucl Med Biol. 2000 Feb;27(2):199-206. doi: 10.1016/s0969-8051(99)00094-3.

Abstract

The anti-human epidermal growth factor receptor (EGF-R) humanized antibody h-R3 (IgG(1)), which binds to an extracellular domain of EGF-R, was used to evaluate the biodistribution on nude mice xenografted with A431 epidermoid carcinoma cell line. Results are compared with its murine version ior egf/r3 monoclonal antibody (mAb). Twenty-one athymic female 4NMRI nu/nu mice were injected intravenously with 10 microg/100 microCi of (99m)Tc-labeled mAbs. The mAb ior C5 that recognizes an antigen expressed preferentially on the surface of malignant and cytoplasm of normal colorectal cells was used as negative control. Immunoreactivity of (99m)Tc-labeled mAbs was measured by enzyme linked immunosorbent assay on A431 cell line and the immunoreactive fractions determined by Lindmo method. Among all organs significative accumulation was found in tumor (6.14 +/- 2.50 %ID/g, 5.06 +/- 2.61 %ID/g for murine and humanized mAbs, respectively) 4 h after injection. The immunoreactive fractions were found to be 0.88 and 0.81 for murine and humanized mAb, respectively. Thus, we expect better results using the humanized mAb h-R3 for diagnostic immunoscintigraphy.

摘要

抗人表皮生长因子受体(EGF-R)人源化抗体h-R3(IgG(1))可与EGF-R的细胞外结构域结合,用于评估其在接种了A431表皮样癌细胞系的裸鼠体内的生物分布。将结果与其鼠源版本ior egf/r3单克隆抗体(mAb)进行比较。21只无胸腺雌性4NMRI nu/nu小鼠静脉注射10μg/100μCi的(99m)Tc标记的单克隆抗体。识别正常结肠直肠细胞的细胞质和恶性细胞表面优先表达的抗原的mAb ior C5用作阴性对照。通过酶联免疫吸附测定法在A431细胞系上测量(99m)Tc标记的单克隆抗体的免疫反应性,并通过Lindmo方法确定免疫反应分数。注射后4小时,在所有器官中均发现肿瘤中有明显的聚集(鼠源和人源化单克隆抗体分别为6.14±2.50 %ID/g和5.06±2.61 %ID/g)。发现鼠源和人源化单克隆抗体的免疫反应分数分别为0.88和0.81。因此,我们期望使用人源化单克隆抗体h-R3进行诊断性免疫闪烁显像能获得更好的结果。

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