Chen Jinjin, Qiu Min, Ye Zhongfeng, Nyalile Thomas, Li Yamin, Glass Zachary, Zhao Xuewei, Yang Liu, Chen Jianzhu, Xu Qiaobing
Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sci Adv. 2021 May 5;7(19). doi: 10.1126/sciadv.abf1244. Print 2021 May.
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.
原位疫苗接种因其便利性和诱导多种肿瘤抗原的能力，是一种很有前景的癌症免疫治疗策略。然而，肿瘤抗原的低交叉呈递和免疫抑制性肿瘤微环境阻碍了原位疫苗接种技术的发展。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），以同时增强交叉呈递和STING激活。通过组合文库筛选，我们鉴定出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。瘤内注射93-O17S-F/cGAMP并联合阿霉素预处理表现出优异的抗肿瘤疗效，35%的小鼠原发性B16F10肿瘤完全消退，71%的小鼠在后续攻击中完全恢复，表明诱导了针对肿瘤的免疫记忆。本研究为原位癌症疫苗接种提供了一种很有前景的策略。
