Nestor Marika, Ekberg Tomas, Dring John, van Dongen Guus A M S, Wester Kenneth, Tolmachev Vladimir, Anniko Matti
Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Tumour Biol. 2007;28(5):253-63. doi: 10.1159/000110898. Epub 2007 Nov 9.
In the growing field of tumor targeting, there is an urgent need to profile suitable molecular targets. In this study, CD44v6 and EGFR expression was quantified in samples of patients with head and neck squamous cell carcinoma (HNSCC) using a single-dose (SD) radioimmunoassay.
The SD radioimmunoassay using 125I-chimeric monoclonal antibody (cMAb) U36 and 125I-cMAb cetuximab was first validated and then applied to quantify the expression of their target antigen molecules, CD44v6 and EGFR, in patient samples. Results were compared to immunohistochemical staining.
The SD assay provided sensitive quantitative values of the molecular targets studied, generally agreeing with the immunohistochemistry (IHC) results. The results indicated that expression of CD44v6 (0.2-20 nmol/mug membrane) was generally higher than that of EGFR (0.6-2.3 nmol/microg membrane) in the tumor samples analyzed, which corresponded to an average of 700,000 and 90,000 antigen molecules per cell, respectively.
The SD radioimmunoassay is simple, reliable, and can be performed on a small amount (50 mg) of tissue. This assay could be a useful tool in the growing field of personalized cancer therapy, and can be used as a complement to IHC. In the tumors studied, CD44v6 was generally expressed at a higher level than EGFR, which might suggest that it could be more readily targeted by MAbs.
在肿瘤靶向治疗这个不断发展的领域,迫切需要确定合适的分子靶点。在本研究中,使用单剂量(SD)放射免疫分析法对头颈部鳞状细胞癌(HNSCC)患者样本中的CD44v6和表皮生长因子受体(EGFR)表达进行了定量分析。
首先对使用125I嵌合单克隆抗体(cMAb)U36和125I-cMAb西妥昔单抗的SD放射免疫分析法进行验证,然后将其应用于定量分析患者样本中其靶抗原分子CD44v6和EGFR的表达。将结果与免疫组织化学染色结果进行比较。
SD分析法提供了所研究分子靶点的敏感定量值,总体上与免疫组织化学(IHC)结果一致。结果表明,在所分析的肿瘤样本中,CD44v6的表达(0.2 - 20 nmol/μg膜)通常高于EGFR的表达(0.6 - 2.3 nmol/μg膜),分别对应于每个细胞平均700,000和90,000个抗原分子。
SD放射免疫分析法简单、可靠,可在少量(50 mg)组织上进行。该分析法可能是不断发展的个性化癌症治疗领域中的一种有用工具,可作为免疫组织化学的补充。在所研究的肿瘤中,CD44v6的表达通常高于EGFR,这可能表明它更容易被单克隆抗体靶向。