Weiner G J, Liu H M, Wooldridge J E, Dahle C E, Krieg A M
Department of Internal Medicine, University of Iowa, University of Iowa Cancer Center, University of Iowa Graduate Program in Immunology, and Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, USA.
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10833-7. doi: 10.1073/pnas.94.20.10833.
Recent advances in our understanding of the immune response are allowing for the logical design of new approaches to cancer immunization. One area of interest is the development of new immune adjuvants. Immunostimulatory oligodeoxynucleotides containing the CpG motif (CpG ODN) can induce production of a wide variety of cytokines and activate B cells, monocytes, dendritic cells, and NK cells. Using the 38C13 B cell lymphoma model, we assessed whether CpG ODN can function as immune adjuvants in tumor antigen immunization. The idiotype served as the tumor antigen. Select CpG ODN were as effective as complete Freund's adjuvant at inducing an antigen-specific antibody response but were associated with less toxicity. These CpG ODN induced a higher titer of antigen-specific IgG2a than did complete Freund's adjuvant, suggesting an enhanced TH1 response. Mice immunized with CpG ODN as an adjuvant were protected from tumor challenge to a degree similar to that seen in mice immunized with complete Freund's adjuvant. We conclude that CpG ODN are effective as immune adjuvants and are attractive as part of a tumor immunization strategy.
我们对免疫反应认识的最新进展使得合理设计癌症免疫新方法成为可能。一个受关注的领域是新型免疫佐剂的开发。含CpG基序的免疫刺激寡脱氧核苷酸(CpG ODN)可诱导多种细胞因子的产生,并激活B细胞、单核细胞、树突状细胞和自然杀伤细胞。利用38C13 B细胞淋巴瘤模型,我们评估了CpG ODN在肿瘤抗原免疫中是否能作为免疫佐剂发挥作用。独特型作为肿瘤抗原。所选的CpG ODN在诱导抗原特异性抗体反应方面与完全弗氏佐剂一样有效,但毒性较小。这些CpG ODN诱导的抗原特异性IgG2a滴度高于完全弗氏佐剂,表明TH1反应增强。用CpG ODN作为佐剂免疫的小鼠在一定程度上受到保护,免受肿瘤攻击,这与用完全弗氏佐剂免疫的小鼠情况相似。我们得出结论,CpG ODN作为免疫佐剂是有效的,作为肿瘤免疫策略的一部分很有吸引力。