Karanikas V, Hwang L A, Pearson J, Ong C S, Apostolopoulos V, Vaughan H, Xing P X, Jamieson G, Pietersz G, Tait B, Broadbent R, Thynne G, McKenzie I F
Immunology and Vaccine Laboratory, The Austin Research Institute, Heidelberg 3084, Victoria, Australia.
J Clin Invest. 1997 Dec 1;100(11):2783-92. doi: 10.1172/JCI119825.
Mucin 1 (MUC1) is a large complex glycoprotein that is highly expressed in breast cancer, and as such could be a target for immunotherapy. In mice, human MUC1 is highly immunogenic, particularly when conjugated to mannan, where a high frequency of CD8(+) MHC-restricted cytotoxic T lymphocytes is induced, accompanied by tumor protection. On this basis, a clinical trial was performed in which 25 patients with advanced metastatic carcinoma of breast, colon, stomach, or rectum received mannan-MUC1 in increasing doses. After 4 to 8 injections, large amounts of IgG1 anti-MUC1 antibodies were produced in 13 out of 25 patients (with antibody titers by ELISA of 1/320-1/20,480). Most of the antibodies reacted to the epitopes STAPPAHG and PAPGSTAP. In addition, T cell proliferation was found in 4 out of 15 patients, and CTL responses were seen in 2 out of 10 patients. Mannan-MUC1 can immunize patients, particularly for antibody formation, and to a lesser extent, cellular responses. It remains to be seen whether such responses have antitumor activity.
黏蛋白1（MUC1）是一种大型复合糖蛋白，在乳腺癌中高度表达，因此可能成为免疫治疗的靶点。在小鼠中，人MUC1具有高度免疫原性，特别是与甘露聚糖偶联时，可诱导高频率的CD8(+) 主要组织相容性复合体（MHC）限制的细胞毒性T淋巴细胞，并伴有肿瘤保护作用。在此基础上，开展了一项临床试验，25例晚期转移性乳腺癌、结肠癌、胃癌或直肠癌患者接受了递增剂量的甘露聚糖-MUC1治疗。在4至8次注射后，25例患者中有13例产生了大量的IgG1抗MUC1抗体（通过酶联免疫吸附测定法（ELISA）测得抗体效价为1/320 - 1/20,480）。大多数抗体与表位STAPPAHG和PAPGSTAP发生反应。此外，15例患者中有4例出现T细胞增殖，10例患者中有2例出现细胞毒性T淋巴细胞（CTL）反应。甘露聚糖-MUC1可使患者产生免疫反应，特别是形成抗体，在较小程度上也能引发细胞反应。这种反应是否具有抗肿瘤活性还有待观察。
