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MF59 联合 CpG ODN 作为重组 HSP65-MUC1 的有效佐剂,在小鼠中诱导抗 MUC1+肿瘤免疫。

MF59 formulated with CpG ODN as a potent adjuvant of recombinant HSP65-MUC1 for inducing anti-MUC1+ tumor immunity in mice.

机构信息

Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China.

出版信息

Int Immunopharmacol. 2012 Aug;13(4):408-16. doi: 10.1016/j.intimp.2012.05.003. Epub 2012 May 14.

Abstract

MF59 is an oil-in-water emulsion adjuvant approved for influenza vaccines for human use in Europe. Due to its Th2 inducing properties, MF59 is seldom tested for cancer vaccines. In this study, MF59 formulated with a C-type CpG oligodeoxynucleotide (YW002) was tested for its Th1 adjuvant activity to induce immune responses to HSP65-MUC1, a recombinant fusion protein incorporating a mycobacterial heat shock protein (HSP65) and mucin 1, cell surface associated (MUC1) derived peptide. Combination of YW002 with MF59 (MF59-YW002) could confer a potent Th1 biasing property to the adjuvant, which enhanced the immunogenicity of HSP65-MUC1 to induce significantly higher levels of specific IgG2c, increased IFN-γ mRNA expression in splenocytes and the generation of antigen-specific cytotoxic T lymphocytes in mice. When prophylactically applied, MF59-YW002 adjuvant containing HSP65-MUC1 inhibited the growth of MUC1+ B16 melanoma and prolonged the survival of tumor-bearing mice. In contrast, adjuvant containing MF59 with HSP65-MUC1 in the absence of YW002, promoted the growth of MUC1+ B16 melanoma in mice. These results suggest that MF59 plus CpG oligodeoxynucleotide might be developed as an efficient adjuvant for tumor vaccines against melanoma, and possibly other tumors.

摘要

MF59 是一种油包水乳剂佐剂,已在欧洲获得批准用于人类流感疫苗。由于其具有 Th2 诱导特性,因此很少针对癌症疫苗进行测试。在这项研究中,用 C 型 CpG 寡脱氧核苷酸(YW002)配制的 MF59 被测试了其作为 Th1 佐剂的活性,以诱导对 HSP65-MUC1 的免疫反应,HSP65-MUC1 是一种包含分枝杆菌热休克蛋白(HSP65)和细胞表面相关(MUC1)衍生肽的重组融合蛋白。YW002 与 MF59 的组合(MF59-YW002)可以赋予佐剂强大的 Th1 偏向性,从而增强 HSP65-MUC1 的免疫原性,诱导明显更高水平的特异性 IgG2c,增加脾细胞中的 IFN-γ mRNA 表达,并在小鼠中产生抗原特异性细胞毒性 T 淋巴细胞。当预防性应用时,含有 HSP65-MUC1 的 MF59-YW002 佐剂抑制了 MUC1+B16 黑色素瘤的生长,并延长了荷瘤小鼠的存活时间。相比之下,含有 MF59 与 HSP65-MUC1 的佐剂而没有 YW002 则促进了 MUC1+B16 黑色素瘤在小鼠中的生长。这些结果表明,MF59 加 CpG 寡脱氧核苷酸可能被开发为针对黑色素瘤和可能其他肿瘤的有效肿瘤疫苗佐剂。

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