异基因型 MHC Ⅱ 类分子转基因表达对小鼠肿瘤细胞的免疫反应

Antitumor immunity induced by retroviral mediated allogeneic major histocompatibility complex class Ⅱ gene transfer in murine tumor models

肿瘤细胞的免疫原性弱而不能引起宿主产生足够强的免疫反应是其逃逸机体免疫监视的重要原因。通过逆转录病毒介导的基因转移技术使异基因型Ｈ－２Ａｄ分子在具有免疫原性的小鼠Ｔ淋巴瘤ＥＬ４和非免疫原性的小鼠黑色素瘤的Ｂ１６细胞中表达。动物实验结果显示：异基因型Ｈ－２Ａｄ基因的转导表达，可使ＥＬ４细胞的致瘤性丧失；使Ｂ１６细胞的致瘤性和实验性转移能力降低。通过转导异基因型Ｈ－２Ａｄ基因的Ｂ１６细胞的免疫接种，可使再次接种的亲本Ｂ１６细胞的致瘤性减弱。结果表明异基因型ＭＨＣⅡ基因的转导表达，可增强肿瘤细胞的免疫原性，诱导机体产生抗肿瘤免疫反应。

Tumor cells may escape immune surveillance for its poor immunogenicity to induce sufficient antitumor immunity.In an effort to enhance the immunogenicity of tumor cells,we introduced murine allogeneic MHC class Ⅱ gene,H 2A d into EL4,a murine immunogenic T lymphoma and B16,a murine nonimmunogenic melanoma.Experiments on syngeneic mice showed that the expression of allogeneic MHC class Ⅱ molecules completely abrogated tumorigenicity of EL4 tumor cells and reduced tumorigenicity and metastasis of B16 tumor cells.In addition,the tumorigenicity of subchallenged or established parental B16 tumor cells could be reduced by vaccination with B16 tumor cells harboring H 2A d.Our results indicate that antitumor immunity could be induced by transducing allogeneic MHC class Ⅱ gene into tumor cells.