CpG ODN与聚肌胞在肿瘤免疫中联合应用的研究  

The Investigation of the Adjuvant Effects of Two Immunological Stimulators——CpG ODN and Poly(I:C)

作　　者：张永明[1] 刘学丽[1] 张子豫[2] 马洁[1] 

机构地区：[1]中国医学科学院北京协和医学院肿瘤医院肿瘤研究所,分子肿瘤学国家重点实验室,北京市100021 [2]潍坊医学院药理教研室

出　　处：《中国全科医学》2008年第10期861-864,共4页Chinese General Practice

基　　金：国家自然科学基金资助(2002AA214131)

摘　　要：目的选择两种新型的生物型免疫刺激剂CpGODN和poly(I:C)联合作为多肽抗原佐剂,通过体外及体内多种免疫功能指标检测,探讨二者联合应用的免疫增效作用。方法体外实验中用CpGODN和poly(I:C)单独或联合与正常小鼠脾细胞混合培养,24h后检测细胞培养上清中细胞因子分泌情况;体内实验中用CpGODN和poly(I:C)单独或者联合作为MUC1多肽抗原的佐剂免疫小鼠,通过ELISA方法检测免疫血清中抗体效价及应用细胞毒性T淋巴细胞杀伤实验对各组间免疫水平的差别进行评价。结果CpGODN与poly(I:C)联合应用体外能有效诱导脾细胞分泌IL-12p40和TNF-α。体内实验联合组小鼠血清中TNF-α和IFN-γ水平升高,IL-4水平降低。小鼠血清中抗MUC1多肽抗体效价各组间差别无统计学意义(P>0·05),但细胞毒性T淋巴细胞(cytotoxicityTlympho-cyte,CTL)杀伤实验显示联合组能有效杀伤靶细胞。结论CpGODN和poly(I:C)联合作为可溶性多肽MUC1的免疫佐剂,与单用相比能有效地增强机体的抗肿瘤免疫应答反应。Objective Poly （I： C） and CpG ODN, which activate immunological reactions, are pathogen -associated molecular patterns of viruses and bacteria respectively. To examine whether the combination of poly （I： C） and CpG ODN could provide enhanced stimulation of innate immunological response and adaptive immunological response, cytokine production of splenocytes were examed when stimulated with poly （ I ： C） and CpG ODN. To detect if there is synergetic effects between the two immunological stimulator as adjuvant of peptides, C57BL/6 were immunized with MUC1 plus poly （I： C） /CpG ODN or the combination of the two agents. Then the serum level of cytokines were detected, Methods In vitro, murine splenocytes were incubated with poly （I： C） alone, CpG ODN alone or the combination of the two agents. Interleukin （IL） -12p40, tumor necrosis factor-α （TNF- α）, IFN -γ and IL -4 in the supernatant were measured by ELISA. In vivo, C57BL/6 mice were received s. c. and i. p. injection with MUC1 peptide, alone or in,combination with CpG ODN, polyI： C, CpG ODN added with polyI： C. The humoral and cellular immune responses were evaluated. Results In vitro, combined treatments demonstrated synergy for interleukin （IL） - 12p40, and TNF - α production. In vivo, immunization of mice with the combination of poly （I： C） and CpG ODN demonstrated synergism in the serum level of TNF -α, IL - 12p40 and IFN -γ. Conclusion The combination of poly （I： C） and CpG ODN as the adjuvant of peptide MUC1, resulted in an enhanced innate and adaptive immune response that could be used for tumor vaccination or immunotherapy. The combination of poly （ I ： C） and CpG ODN could be a potent adjuvant. These data suggest that CpG ODN ＋ poly （ I ： C） codelivery with TAA could be an effective approach to induce stronger protective immune responses as a strategy for curing cancer.

关 键 词：CPG ODN 聚肌胞 MUC1 免疫佐剂 

分 类 号：R979.5[医药卫生—药品]