Snyder Linda A, Goletz Theresa J, Gunn George R, Shi Frank F, Harris Michael C, Cochlin Karyn, McCauley Christine, McCarthy Stephen G, Branigan Patrick J, Knight David M
Centocor Inc., 145 King of Prussia Road, Radnor, PA 19087, USA.
Vaccine. 2006 Apr 12;24(16):3340-52. doi: 10.1016/j.vaccine.2006.01.014. Epub 2006 Jan 19.
MUC1 (mucin 1) is a tumor-associated antigen that is overexpressed in many adenocarcinomas. Active immunotherapy targeting tumors expressing MUC1 could have great treatment value. MUC1 DNA vaccines were evaluated in MUC1 transgenic (MUC1.Tg) mice challenged with MC38/MUC1+ tumor cells. Vaccination with MUC1 plasmid DNA (pMUC1) alone was insufficient to induce tumor protection. However, co-administration of pMUC1 with a plasmid encoding murine interleukin-18 (pmuIL-18) resulted in significant tumor protection and survival after tumor challenge. Protection was durable in the absence of additional vaccination, as demonstrated by continued protection of vaccinated mice following tumor rechallenge. Mice surviving challenges with MC38/MUC1+ cells showed significant protection after challenge with MUC1(-) MC38 tumor cells, suggesting that these mice had developed immune responses to epitopes shared between the tumor cell lines. Antibody-mediated depletion of lymphocyte subsets demonstrated that protection was due largely to CD4+ T cells. This work demonstrates that a naked DNA vaccine can break tolerance to MUC1 and induce an immune response capable of mediating both significant protection from tumor challenge and increased survival.
粘蛋白1（MUC1）是一种肿瘤相关抗原，在许多腺癌中过度表达。针对表达MUC1的肿瘤进行主动免疫治疗可能具有巨大的治疗价值。在受到MC38/MUC1+肿瘤细胞攻击的MUC1转基因（MUC1.Tg）小鼠中评估了MUC1 DNA疫苗。单独用MUC1质粒DNA（pMUC1）接种不足以诱导肿瘤保护作用。然而，将pMUC1与编码小鼠白细胞介素-18的质粒（pmuIL-18）共同给药，在肿瘤攻击后可产生显著的肿瘤保护作用和延长生存期。在没有额外接种疫苗的情况下，保护作用持久，如在肿瘤再次攻击后接种疫苗的小鼠持续受到保护所证明。在受到MC38/MUC1+细胞攻击后存活的小鼠，在受到MUC1（-）MC38肿瘤细胞攻击后显示出显著的保护作用，这表明这些小鼠已对肿瘤细胞系之间共有的表位产生了免疫反应。抗体介导的淋巴细胞亚群耗竭表明，保护作用主要归因于CD4+T细胞。这项研究表明，裸DNA疫苗可以打破对MUC1的耐受性，并诱导一种能够介导显著的肿瘤攻击保护作用和延长生存期的免疫反应。
