CpG ODN联合肿瘤抗原致敏的树突状细胞疫苗抑制和预防小鼠黑色素瘤的研究  

Effect of DC vaccine sensitized with CpG ODN combined with tumor antigen on murine melanoma

作　　者：曾佳昕 张文渊 刘二刚 刘凌云[4] 黄永焯 王慧媛 ZENG Jia-xin;ZHANG Wen-yuan;LIU Er-gang;LIU Ling-yun;HUANG Yong-zhuo;WANG Hui-yuan(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;Zhongshan Branch,the Institute of Drug Research and Development,Chinese Academy of Sciences,Zhongshan 528437,China;The Research Center of Basic Integrative Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510006,China)

机构地区：[1]广州中医药大学第一附属医院,广东广州510405 [2]中国科学院上海药物研究所,上海201203 [3]中国科学院药物创新研究院中山研究院,广东中山528437 [4]广州中医药大学基础医学院,广东广州510006

出　　处：《药学学报》2022年第2期385-391,共7页Acta Pharmaceutica Sinica

基　　金：重点研发计划政府间国际科技创新合作/港澳台科技创新合作重点专项项目(2021YFE0103100);广州市科技计划项目(201707010319);上海市科委一带一路项目(18430740800)。

摘　　要：探讨非甲基化的胞嘧啶鸟嘌呤二核苷酸(CpG)的脱氧寡核苷酸(oligodeoxynucleotide,ODN)联合肿瘤抗原致敏树突状细胞(DC)治疗和预防黑色素瘤的作用。首先从小鼠骨髓中分离得到骨髓来源的树突状细胞(BMDC),并将小鼠黑色素瘤B16细胞来源的全抗原与DC共孵育,采用全硫代修饰的CpG ODN作DC免疫刺激剂,制备DC疫苗。通过测定T淋巴细胞增殖和细胞毒性T淋巴细胞(CTL)对靶细胞B16的杀伤作用来评价该疫苗的体外免疫活性。将疫苗经小鼠腹腔注射,观察其治疗和预防小鼠黑色素瘤的效果。所有动物实验均在中国科学院上海药物研究所实验动物管理委员会(IACUC)的指导和标准下进行。结果显示,CpG ODN和肿瘤抗原联用致敏的DC疫苗能够促进T淋巴细胞增殖,并提高活化的T淋巴细胞对靶细胞B16的杀伤活性。体内实验表明,无论是治疗实验还是预防实验,DC疫苗组的平均瘤重和瘤体积均低于PBS对照组。实验结果证明基于CpG ODN和黑色素瘤肿瘤抗原制备的DC疫苗对肿瘤具有较好的抑制作用,为恶性黑色素瘤治疗提供了一个潜在的方案。The potential application of dendritic cells(DC)sensitized with cytosine-phosphoric acid-guanine(CpG)oligodeoxynucleotide(ODN)and tumor antigen as a vaccine against murine melanoma was investigated with freshly isolated mouse bone marrow-derived dendritic cells.For the DC vaccine preparation,DC were sensitized with the B16 tumor antigen and CpG ODN was used to promote further maturation of the DC.The immunogenic activity of the vaccine was evaluated in vitro by determining the proliferation of T lymphocytes and the killing effect of cytotoxic T lymphocytes(CTL)on B16 tumor cells.The DC vaccine was injected intraperitoneally and tumor inhibition in mice bearing B16 xenografts was examined.All mice were cared for under an approved SIMM Institutional Animal Care and Use Committee(IACUC)protocol.In vitro,this DC vaccine promoted the proliferation of T lymphocytes and showed a potent killing effect on the target B16 cells.In vivo experiments showed that after treatment or pre-immunization both the tumor volume and weight were significantly decreased.The DC vaccine with CpG ODN and tumor antigen exhibited an inhibitory effect against melanoma,providing a potential method for melanoma cancer treatment.

关 键 词：树突状细胞 肿瘤疫苗 CPG寡脱氧核苷酸 黑色素瘤 免疫治疗 

分 类 号：R966[医药卫生—药理学]