中文摘要：研究设计了一种新型的疫苗佐剂，该佐剂由明矾（alum）、CpG寡聚脱氧核苷酸（CpG）和天然防御调节肽HH2组成，该佐剂能够提高机体抗肿瘤免疫反应。与单独使用CpG、HH2相比，CpG-HH2复合佐剂在体外能够显著增强IFN-，TNF-α和NK-β的浓度，提高抗原摄取，增强p38、 Erk1/2和 NF-kappa B的激活。将NYESO-1抗原与明矾-CpG-HH2联合使用能够有效抑制肿瘤发生，降低肿瘤负担。此外，NYESO-1抗原与明矾-CpG-HH2联合使用显著激活了NK细胞毒性，诱导了抗体相关细胞毒性，显著降低了细胞毒性T淋巴细胞反应，增加了肿瘤中的浸润淋巴球。此外，体外培养完全消除了CD8（+）细胞、并消除了部分NK细胞，这阻止了NY-ESO-1-明矾-CpG-HH2免疫后的抗肿瘤活性。
外文摘要：Single-component adjuvant is prone to eliciting a specific type of Th1 or Th2 response. So, the development of combinatorial adjuvants inducing a robust mixed Th1/Th2 response is a promising vaccination strategy against cancer. Here, we describe a novel combination of aluminum salts (alum), CpG oligodeoxynucleotide (CpG) and innate defense regulator peptide HH2 for improving anti-tumor immune responses. The CpG-HH2 complex significantly enhanced the production of IFN-., TNF-a and IL-1 beta, promoted the uptake of antigen and strengthened the activation of p38, Erk1/2 and NF-kappa B in vitro, compared to CpG or HH2 alone. Immunization with NYESO-1 antigen plus alum-CpG-HH2 combinatorial adjuvant effectively inhibited tumor growth and reduced tumor burden in prophylactic and therapeutic tumor models and even in passive serum or cellular therapy. In addition, co-administration of NY-ESO-1 with alum-CpG-HH2 combinatorial adjuvant markedly activated NK cell cytotoxicity, induced antibody-dependent cellular cytotoxicity (ADCC), dramatically elicited cytotoxic T lymphocytes (CTLs) response, and increased infiltrating lymphocytes in tumors. Moreover, in vivo depletion of CD8(+) T cells completely and depletion of NK cells partially blocked the anti-tumor activity of NY-ESO-1-alum-CpG-HH2 immunization. Overall, our results demonstrate a novel adjuvant combination for cancer vaccine with efficient immunomodulation by stimulating innate immunity and mediating adaptive immunity.
外文关键词：combinatorial adjuvant； aluminum salts； CpG oligodeoxynucleotide； innate defense regulator peptide HH2； anti-tumor immune responses
作者：Tian, YM; Li, M; Yu, CH; Zhang, R; Zhang, XY; Huang, R; Lu, L; Yuan, FJ; Fan, YZ; Zhou, BL; Men, K; Xu, H; Yang, L
作者单位：四川大学
期刊名称：ONCOTARGET
期刊影响因子：5.022
出版年份：2017
出版刊次：7
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