Gene-guided OX40L anchoring to tumor cells for synergetic tumor“self-killing”immunotherapy  

作　　者：Lin Lin Yingying Hu Zhaopei Guo Jie Chen Pingjie Sun Huayu Tian Xuesi Chen 

机构地区：[1]Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun,130022,PR China [2]University of Science and Technology of China,Hefei,230026,PR China [3]College of Chemistry and Chemical Engineering,Xiamen University,Xiamen,361005,PR China

出　　处：《Bioactive Materials》2023年第7期689-700,共12页生物活性材料（英文）

基　　金：This work was financially supported by the National Key R&D Program of China(2021YFB3800900);National Natural Science Foundation of China(51925305,51873208,51833010,51803210,51973217);Jilin province science and technology development program(20200201075JC).

摘　　要：The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade(ICB)therapy.Here,a tumor“self-killing”therapy based on gene-guided OX40L anchoring to tumor cell membrane was reported to boost ICB therapy.We developed a highly efficient delivery system HA/PEI-KT(HKT)to co-deliver the OX40L plasmids and unmethylated CG-enriched oligodeoxynucleotide(CpG).On the one hand,CpG induced the expression of OX40 on T cells within tumors.On the other hand,OX40L plasmids achieved the OX40L anchoring on the tumor cell membrane to next promote T cells responses via OX40/OX40L axis.Such synergistic tumor“self-killing”strategy finally turned“cold”tumors to“hot”,to sensitize tumors to programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1)blockade therapy,and promoted an immune-mediated tumor regression in both B16F10 and 4T1 tumor models,with prevention of tumor recurrence and metastasis.To avoid the side effects,the gene-guided OX40L anchoring and PD-L1 silencing was proposed to replace the existing antibody therapy,which showed negligible toxicity in vivo.Our work provided a new possibility for tumor“self-killing”immunotherapy to treated various solid tumors.

关 键 词：OX40L anchoring to tumor cell membrane Gene engineering Tumor immunotherapy Anti-PD therapy Tumor relapse and metastasis 

分 类 号：R730.51[医药卫生—肿瘤]