The novel complex combination of alum, CpG ODN and HH2 as adjuvant in cancer vaccine effectively suppresses tumor growth in vivo.
The novel complex combination of alum, CpG ODN and HH2 as adjuvant in cancer vaccine effectively suppresses tumor growth in vivo.
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DOI：
10.18632/oncotarget.17504
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发表时间：
2017-07-11
期刊：
影响因子：
--
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Tian Y;Li M;Yu C;Zhang R;Zhang X;Huang R;Lu L;Yuan F;Fan Y;Zhou B;Men K;Xu H;Yang L
单组分佐剂易于引发特定类型的Th 1或Th 2应答。因此，开发诱导稳健的混合Th 1/Th 2应答的组合佐剂是一种有前途的抗癌疫苗接种策略。在这里，我们描述了铝盐（明矾）、CpG寡脱氧核苷酸（CpG）和先天防御调节肽HH 2的新型组合，用于改善抗肿瘤免疫反应。与单独使用CpG或HH 2相比，CpG-HH 2复合物在体外可显著增强IFN-γ、TNF-α和IL-1β的产生，促进抗原的摄取，并增强p38、Erk 1/2和NF-κB的活化。用NY-ESO-1抗原加alum-CpG-HH 2组合佐剂免疫有效地抑制了肿瘤生长，并在预防性和治疗性肿瘤模型中降低了肿瘤负荷，甚至在被动血清或细胞治疗中也是如此。此外，NY-ESO-1与alum-CpG-HH 2组合佐剂的共施用显著激活NK细胞的细胞毒性，诱导抗体依赖性细胞毒性（ADCC），显著引发细胞毒性T淋巴细胞（CTL）应答，并增加肿瘤中的浸润淋巴细胞。此外，体内完全去除CD 8 + T细胞和部分去除NK细胞阻断NY-ESO-1-alum-CpG-HH 2免疫的抗肿瘤活性。总之，我们的结果证明了一种新型的癌症疫苗佐剂组合，通过刺激先天免疫和介导适应性免疫来有效地调节免疫。
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-γ, TNF-α and IL-1β, promoted the uptake of antigen and strengthened the activation of p38, Erk1/2 and NF-κB in vitro, compared to CpG or HH2 alone. Immunization with NY-ESO-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.
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影响因子：
9.7
作者：
Jordan M;Waxman DJ
通讯作者：
Waxman DJ
影响因子：
3.8
作者：
Iida S;Kuni-Kamochi R;Mori K;Misaka H;Inoue M;Okazaki A;Shitara K;Satoh M
通讯作者：
Satoh M
影响因子：
17.1
作者：
Dhodapkar MV;Sznol M;Zhao B;Wang D;Carvajal RD;Keohan ML;Chuang E;Sanborn RE;Lutzky J;Powderly J;Kluger H;Tejwani S;Green J;Ramakrishna V;Crocker A;Vitale L;Yellin M;Davis T;Keler T
通讯作者：
Keler T
影响因子：
7.3
作者：
Mentlik James A;Cohen AD;Campbell KS
通讯作者：
Campbell KS
影响因子：
5.6
作者：
Amcheslavsky, A;Bar-Shavit, Z
通讯作者：
Bar-Shavit, Z