Nakane P K, Watanabe T
J Histochem Cytochem. 1984 Aug;32(8):894-8. doi: 10.1177/32.8.6747276.
When the subcellular distribution of secretory component (SC) and carcinoembryonic antigen (CEA) were determined immunoelectronmicroscopically, SC was found on the baso-lateral surface and CEA on the apical surface of the normal gastrointestinal epithelium. In contrast, on the neoplastic cells SC and/or CEA were found all around the cell surface. Taking the change in the distribution of CEA on the neoplastic cells as an advantage, an attempt was made to develop an immunotherapeutic method for adenocarcinoma. The method was based upon an assumption that intravenously injected anti-CEA is not accessible to normal epithelial cells, since the tight junction will act as a barrier for the diffusion of antibodies from the interstitium to the apical cell surface, but the anti-CEA will form immunecomplexes with the CEA on the baso-lateral surface of neoplastic cells. Specifically, CEA-producing human gall bladder carcinoma were transplanted into nude mice. To the tumor-bearing mice, glucose oxidase-labeled anti-CEA was intravenously injected. As a control, glucose oxidase-labeled normal rabbit IgG was injected. This was followed with an injection of NaI. It was found that in those mice injected with the labeled anti-CEA, the size of tumor was reduced as much as 30% within three days. In the controls, the tumor continued to grow. In those injected with the labeled anti-CEA, CEA-anti-CEA immunecomplexes were deposited on the glomerular basement membrane, consequently a search for an insoluble apical antigen is currently made.
当采用免疫电子显微镜法测定分泌成分(SC)和癌胚抗原(CEA)的亚细胞分布时,发现正常胃肠道上皮细胞的基底外侧表面有SC,顶端表面有CEA。相反,在肿瘤细胞上,SC和/或CEA存在于细胞表面各处。利用肿瘤细胞上CEA分布的变化,尝试开发一种腺癌免疫治疗方法。该方法基于这样一种假设:静脉注射的抗CEA无法到达正常上皮细胞,因为紧密连接会作为抗体从间质扩散到顶端细胞表面的屏障,但抗CEA会与肿瘤细胞基底外侧表面的CEA形成免疫复合物。具体而言,将产生CEA的人胆囊癌移植到裸鼠体内。给荷瘤小鼠静脉注射葡萄糖氧化酶标记的抗CEA。作为对照,注射葡萄糖氧化酶标记的正常兔IgG。随后注射NaI。结果发现,在注射标记抗CEA的小鼠中,肿瘤大小在三天内缩小了多达30%。在对照组中,肿瘤继续生长。在注射标记抗CEA的小鼠中,CEA-抗CEA免疫复合物沉积在肾小球基底膜上,因此目前正在寻找一种不溶性顶端抗原。