Kuroki M, Murakami M, Wakisaka M, Krop-Watorek A, Oikawa S, Nakazato H, Kosaki G, Matsuoka Y
First Department of Biochemistry, School of Medicine, Fukuoka University.
Jpn J Cancer Res. 1992 May;83(5):505-14. doi: 10.1111/j.1349-7006.1992.tb01957.x.
We have previously reported that a group of monoclonal antibodies (MAbs) to carcinoembryonic antigen (CEA), designated Group F MAbs, are able to discriminate CEA in tumor tissues from normal fecal antigen-2, a soluble form CEA-counterpart in normal adult feces, and that the protein epitopes recognized by them are present on the domain A3-B3 of the CEA molecule. In this study, we further investigated the molecular localization of the epitopes recognized by the Group F MAbs using three new recombinant CEA proteins with restricted domain structures expressed in Chinese hamster ovary cells, and found that the epitopes for the Group F MAbs are present on domain B3 close to the anchoring device of the CEA molecule. The epitopes for the Group F MAbs were retained on the CEA molecules in the plasma of patients with malignant tumors and on the CEA molecules spontaneously released into the culture media from established tumor cell lines. However, a large part of the CEA molecules in the plasma of normal individuals were found to lack the epitopes for the Group F MAbs. These results provide a basis for the improved cancer diagnosis by using our CEA assay system utilizing a Group F MAb, and indicate the potential clinical utility of the Group F MAbs.
我们之前曾报道过,一组针对癌胚抗原(CEA)的单克隆抗体(MAb),即F组单克隆抗体,能够区分肿瘤组织中的CEA与正常粪便抗原-2(正常成人粪便中一种可溶性形式的CEA对应物),并且它们所识别的蛋白质表位存在于CEA分子的A3-B3结构域上。在本研究中,我们使用三种在中国仓鼠卵巢细胞中表达的具有受限结构域的新型重组CEA蛋白,进一步研究了F组单克隆抗体所识别表位的分子定位,发现F组单克隆抗体的表位存在于靠近CEA分子锚定装置的B3结构域上。F组单克隆抗体的表位保留在恶性肿瘤患者血浆中的CEA分子上,以及在已建立的肿瘤细胞系自发释放到培养基中的CEA分子上。然而,发现正常个体血浆中的大部分CEA分子缺乏F组单克隆抗体的表位。这些结果为使用我们基于F组单克隆抗体的CEA检测系统改进癌症诊断提供了依据,并表明了F组单克隆抗体的潜在临床应用价值。