Induction of antitumor immunity by vaccination of dendritic cells transfected with MUC1 RNA
Induction of antitumor immunity by vaccination of dendritic cells transfected with MUC1 RNA
复制标题
DOI：
10.4049/jimmunol.165.10.5713
复制
发表时间：
2000-11-15
影响因子：
4.4
通讯作者：
Gong, JL
中科院分区：
文献类型：
--
作者：
Koido, S;Kashiwaba, M;Gong, JL
树突状细胞（DC）是一种功能强大的APC。本研究用编码MUC 1抗原的RNA转染小鼠骨髓来源的DC，MUC 1抗原在人乳腺癌和其他肿瘤中异常过表达。MUC 1 RNA转染的DC在细胞表面表达MUC 1和共刺激分子，尾根部注射后，免疫组化双标染色可见转染的DC在腹股沟淋巴结内表达。用MUC 1 RNA转染的DC接种野生型小鼠诱导了针对MUC 1阳性MC 38/MUC 1的抗MUC 1免疫应答，但不诱导针对MUC 1阴性肿瘤细胞的抗MUC 1免疫应答。用转染的DC免疫的小鼠对MC 38/MUC 1肿瘤细胞的攻击具有保护作用，并且在接受疫苗接种后清除了已建立的MC 38/MUC 1肿瘤的小鼠。从用转染的DC免疫的小鼠中分离的CTL表现出对MC 38/MUC 1肿瘤细胞的特异性细胞溶解活性。与这些发现相反，在MUC 1转基因（MUC1.Tg）小鼠中，用转染的DC诱导的抗MUC 1免疫几乎不存在。然而，共施用转染的DC和IL-12逆转了MUC1.Tg小鼠中对MUC 1 Ag的无反应性，并诱导MUC 1特异性免疫应答。这些发现表明，接种用MUC 1 RNA和IL-12转染的DC逆转了对MUC 1的耐受性，并诱导针对MUC 1阳性肿瘤的免疫。
Dendritic cells (DC) are potent APCs, In this study, murine bone marrow-derived DC were transfected with RNA encoding the MUC1 Ag that is aberrantly overexpressed in human breast and other carcinomas. The MUC1 RNA-transfected DC exhibited cell surface expression of MUC1 and costimulatory molecules, After injection at the base of the tail, the transfected DC were detectable in inguinal lymph nodes by dual immunochemical staining. Vaccination of wild-type mice with MUC1 RNA-transfected DC induced anti-MUC1 immune responses against MUC1-positive MC38/MUC1, but not MUC1-negative, tumor cells. Mice immunized with the transfected DC were protected against challenge with MC38/MUC1 tumor cells, Furthermore, mice with established MC38/MUC1 tumors were eliminated after receiving the vaccination. CTLs isolated from mice immunized with the transfected DC exhibited specific cytolytic activity against MC38/MUC1 tumor cells. In contrast to these findings, there was little if any anti-MUC1 immunity induced with the transfected DC in MUC1 transgenic (MUC1.Tg) mice. However, coadministration of the transfected DC and IL-12 reversed the unresponsiveness to MUC1 Ag in MUC1.Tg mice and induced MUC1-specific immune responses, These findings demonstrate that vaccination of DC transfected with MUC1 RNA and IL-12 reverses tolerance to MUC1 and induces immunity against MUC1-positive tumors.