CD47KO/CRT dual-bioengineered cell membrane-coated nanovaccine combined with anti-PD-L1 antibody for boosting tumor immunotherapy  

作　　者：Shengyang Liu Jiayan Wu Yuanji Feng Xiaoya Guo Tong Li Meng Meng Jie Chen Daquan Chen Huayu Tian 

机构地区：[1]School of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai,264005,PR China [2]Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun,130022,PR China [3]College of Chemistry and Chemical Engineering,Xiamen University,Xiamen,361005,PR China

出　　处：《Bioactive Materials》2023年第4期211-224,共14页生物活性材料（英文）

基　　金：The authors are thankful to the National Key R&D Program of China(2021YFB3800900);National Natural Science Foundation of China(51925305,51873208,51973217);Taishan Scholar Foundation of Shandong Province(qnts20161035);Natural Science Foundation of Shandong Province(ZR2019ZD24,ZR2019YQ30);Jilin Province Science and Technology Development Program(20200201075JC,20210509005RQ).

摘　　要：Tumor vaccines trigger tumor-specific immune responses to prevent or treat tumors by activating the hosts’immune systems,and therefore,these vaccines have potential clinical applications.However,the low immunogenicity of the tumor antigen itself and the low efficiency of the vaccine delivery system hinder the efficacy of tumor vaccines that cannot produce high-efficiency and long-lasting antitumor immune effects.Here,we constructed a nanovaccine by integrating CD47KO/CRT dual-bioengineered B16F10 cancer cell membranes and the unmethylated cytosine-phosphate-guanine(CpG)adjuvant.Hyperbranched PEI25k was used to load unmethylated cytosine-phosphate-guanine(CpG)through electrostatic adsorption to prepare PEI25k/CpG nanoparticles(PEI25k/CpG-NPs).CD47KO/CRT dual-bioengineered cells were obtained by CRISPR-Cas9 gene editing technology,followed by the cell surface translocation of calreticulin(CRT)to induce immunogenic cell death(ICD)in vitro.Finally,the extracted cell membranes were coextruded with PEI25k/CpG-NPs to construct the CD47KO/CRT dual-bioengineered cancer cell membrane-coated nanoparticles(DBE@CCNPs).DBE@CCNPs could promote endocytosis of antigens and adjuvants in murine bone marrow derived dendritic cells(BMDCs)and induce their maturation and antigen cross-presentation.To avoid immune checkpoint molecule-induced T cell dysfunction,the immune checkpoint inhibitor,the anti-PD-L1 antibody,was introduced to boost tumor immunotherapy through a combination with the DBE@CCNPs nanovaccine.This combination therapy strategy can significantly alleviate tumor growth and may open up a potential strategy for clinical tumor immunotherapy.

关 键 词：CRISPR-Cas9 Dual-bioengineered cell membrane Immune checkpoint blockade NANOVACCINE Tumor immunotherapy 

分 类 号：R730.51[医药卫生—肿瘤]