In situ cancer vaccination using lipidoid nanoparticles.
In situ cancer vaccination using lipidoid nanoparticles.
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DOI：
10.1126/sciadv.abf1244
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发表时间：
2021-05
期刊：
影响因子：
13.6
通讯作者：
Xu Q
中科院分区：
文献类型：
--
作者：
Chen J;Qiu M;Ye Z;Nyalile T;Li Y;Glass Z;Zhao X;Yang L;Chen J;Xu Q
脂质纳米颗粒原位癌疫苗可增强抗原交叉呈递和STING激活。原位疫苗接种是一种很有前途的癌症免疫治疗策略，因为它方便和能够诱导大量的肿瘤抗原。然而，原位疫苗接种技术的进步一直受到肿瘤抗原交叉呈递率低和免疫抑制肿瘤微环境的阻碍。为了平衡原位疫苗接种的安全性和有效性，我们设计了一种脂质纳米颗粒（LNP）来同时增强交叉呈现和STING激活。通过组合文库筛选，我们确定了93-O17S-F，它既能促进肿瘤抗原的交叉呈递，又能促进cGAMP （STING激动剂）的细胞内递送。肿瘤内注射93-O17S-F/cGAMP联合预处理阿霉素显示出出色的抗肿瘤效果，35%的小鼠从原发性B16F10肿瘤中完全恢复，71%的小鼠从随后的攻击中完全恢复，这表明诱导了对肿瘤的免疫记忆。本研究为原位癌疫苗接种提供了一个有希望的策略。
In situ cancer vaccination by lipidoid nanoparticles enhances antigen cross-presentation and STING activation. In situ vaccination is a promising strategy for cancer immunotherapy owing to its convenience and the ability to induce numerous tumor antigens. However, the advancement of in situ vaccination techniques has been hindered by low cross-presentation of tumor antigens and the immunosuppressive tumor microenvironment. To balance the safety and efficacy of in situ vaccination, we designed a lipidoid nanoparticle (LNP) to achieve simultaneously enhancing cross-presentation and STING activation. From combinatorial library screening, we identified 93-O17S-F, which promotes both the cross-presentation of tumor antigens and the intracellular delivery of cGAMP (STING agonist). Intratumor injection of 93-O17S-F/cGAMP in combination with pretreatment with doxorubicin exhibited excellent antitumor efficacy, with 35% of mice exhibiting total recovery from a primary B16F10 tumor and 71% of mice with a complete recovery from a subsequent challenge, indicating the induction of an immune memory against the tumor. This study provides a promising strategy for in situ cancer vaccination.
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DOI：
10.1002/adma.202001808
发表时间：
2020-07
期刊：
Advanced materials (Deerfield Beach, Fla.)
影响因子：
--
作者：
Jiang Y;Krishnan N;Zhou J;Chekuri S;Wei X;Kroll AV;Yu CL;Duan Y;Gao W;Fang RH;Zhang L
通讯作者：
Zhang L
影响因子：
38.3
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
通讯作者：
Gao J
影响因子：
38.3
作者：
Min Y;Roche KC;Tian S;Eblan MJ;McKinnon KP;Caster JM;Chai S;Herring LE;Zhang L;Zhang T;DeSimone JM;Tepper JE;Vincent BG;Serody JS;Wang AZ
通讯作者：
Wang AZ
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
温和的光热疗法通过一体化和全控策略增强免疫冷肿瘤的抗 PD-L1 治疗
影响因子：
16.6
作者：
Huang, Liping;Li, Yanan;Sun, Chunmeng
通讯作者：
Sun, Chunmeng