A STING-activating nanovaccine for cancer immunotherapy.
A STING-activating nanovaccine for cancer immunotherapy.
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DOI：
10.1038/nnano.2017.52
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发表时间：
2017-07
影响因子：
38.3
通讯作者：
Gao J
中科院分区：
文献类型：
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作者：
Luo M;Wang H;Wang Z;Cai H;Lu Z;Li Y;Du M;Huang G;Wang C;Chen X;Porembka MR;Lea J;Frankel AE;Fu YX;Chen ZJ;Gao J
肿瘤特异性T细胞的产生对于癌症免疫治疗至关重要。实现稳健的T细胞应答的主要挑战是抗原呈递细胞（APC）中抗原交叉呈递与先天刺激的时空协调。在这里，我们报告了一种最低限度的纳米疫苗，通过抗原与合成聚合物纳米颗粒PC 7A NP的简单物理混合物，产生了强烈的细胞毒性T细胞反应，全身细胞因子表达较低。从机制上讲，PC 7A NP实现了肿瘤抗原向引流淋巴结中的APC的有效胞质递送，导致表面呈递增加，同时激活I型干扰素刺激的基因。这种作用依赖于STING，而不是Toll样受体或MAVS通路。纳米疫苗在黑色素瘤、结肠癌和人乳头瘤病毒-E6/E7肿瘤模型中产生了有效的肿瘤生长抑制作用。PC 7A纳米疫苗与抗PD-1抗体的组合在TC-1肿瘤模型中显示出极大的协同作用，在60天内具有100%的存活率。用TC-1细胞重新激发这些无肿瘤动物导致肿瘤生长的完全抑制，表明产生了长期抗肿瘤记忆。STING激活纳米疫苗为癌症免疫治疗提供了一种简单，安全和强大的增强抗肿瘤免疫力的策略。
Generation of tumor-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T cell response is the spatio-temporal orchestration of antigen cross-presentation in antigen presenting cells (APCs) with innate stimulation. Here we report a minimalist nanovaccine by a simple physical mixture of an antigen with a synthetic polymeric nanoparticle, PC7A NP, which generated a strong cytotoxic T cell response with low systemic cytokine expression. Mechanistically, PC7A NP achieved efficient cytosolic delivery of tumor antigens to APCs in draining lymph nodes leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes. This effect was dependent on STING but not Toll-like receptor or MAVS pathway. Nanovaccine produced potent tumor growth inhibition in melanoma, colon cancer, and human papilloma virus-E6/E7 tumor models. Combination of PC7A nanovaccine with an anti-PD-1 antibody showed great synergy with 100% survival over 60 days in a TC-1 tumor model. Rechallenging of these tumor-free animals with TC-1 cells led to complete inhibition of tumor growth, suggesting generation of long-term antitumor memory. The STING-activating nanovaccine offers a simple, safe and robust strategy in boosting anti-tumor immunity for cancer immunotherapy.
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DOI：
10.1126/science.1244040
发表时间：
2013-09-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li XD;Wu J;Gao D;Wang H;Sun L;Chen ZJ
通讯作者：
Chen ZJ
影响因子：
15
作者：
Ma, Xinpeng;Wang, Yiguang;Zhao, Tian;Li, Yang;Su, Lee-Chun;Wang, Zhaohui;Huang, Gang;Sumer, Baran D.;Gao, Jinming
通讯作者：
Gao, Jinming
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
DOI：
10.1073/pnas.1408686111
发表时间：
2015-01-13
影响因子：
11.1
作者：
Maldonado, Roberto A.;LaMothe, Robert A.;Kishimoto, Takashi Kei
通讯作者：
Kishimoto, Takashi Kei
影响因子：
64.8
作者：
通讯作者：
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