Hinoda Y, Imai K
Dept. of Internal Medicine (Section 1), Sapporo Medical University School of Medicine.
Gan To Kagaku Ryoho. 1994 Feb;21(2):150-6.
Recent molecular biological approach has revealed the primary structure of some mucin core proteins. Most prominent characteristic is tandemly repeated sequences. cDNA cloning of 6 kinds of mucin core proteins, MUC1-6, have thus been performed. Among them, the entire structure was revealed on MUC1 and 2. MUC 1 is a type I transmembrane protein with a large number of tandem repeat consisting of 20 amino acids. We have found that mouse MoAb MUSE11 against adenocarcinoma, which detects circulating MUC1 in patients with gastrointestinal and pancreatic cancers, recognizes part of the tandem repeat of MUC1 using synthetic peptides. To date, some of the MoAbs to adenocarcinoma which were prepared for the last decade have been shown to react with the tandem repeat of MUC1(MUC1 epitope), suggesting that MUC1 epitope could be highly immunogenic in human. Recently, cytotoxic T-cells against MUC1 epitope were established from breast and pancreas cancer patients. We could also induce those T-cells from the patient with multiple myeloma. Interestingly, CTL functions in a HLA-unrestricted manner, and may be of use as an adoptive immunotherapy. In addition, we have found antibody against MUC1 epitope in patients with ulcerative colitis or colon cancer. EB virus-transformed B-cell clone producing antibody against MUC1 epitope has been established from a cancer patient. Thus, MUC1 is now considered as a targeting molecule for immunotherapy. Indeed, Longenecker's group in Canada has recently tried the basic evaluation for immunotherapy using synthetic peptides of MUC1.
最近的分子生物学方法揭示了一些粘蛋白核心蛋白的一级结构。最显著的特征是串联重复序列。因此，已经对6种粘蛋白核心蛋白MUC1 - 6进行了cDNA克隆。其中，MUC1和2的完整结构已被揭示。MUC1是一种I型跨膜蛋白，具有大量由20个氨基酸组成的串联重复序列。我们发现，针对腺癌的小鼠单克隆抗体MUSE11可检测胃肠道和胰腺癌患者循环中的MUC1，它利用合成肽识别MUC1串联重复序列的一部分。迄今为止，过去十年制备的一些针对腺癌的单克隆抗体已被证明可与MUC1的串联重复序列（MUC1表位）发生反应，这表明MUC1表位在人类中可能具有高度免疫原性。最近，从乳腺癌和胰腺癌患者中建立了针对MUC1表位的细胞毒性T细胞。我们也能从多发性骨髓瘤患者中诱导出这些T细胞。有趣的是，细胞毒性T细胞以HLA非限制性方式发挥作用，可能可用作过继性免疫疗法。此外，我们在溃疡性结肠炎或结肠癌患者中发现了针对MUC1表位的抗体。已从一名癌症患者中建立了产生针对MUC1表位抗体的EB病毒转化B细胞克隆。因此，MUC1现在被认为是免疫治疗的靶向分子。事实上，加拿大的朗格内克团队最近尝试了使用MUC1合成肽进行免疫治疗的基础评估。
