In situ vaccination and gene-mediated PD-L1 blockade for enhanced tumor immunotherapy |
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| Authors: | Yingying Hu Lin Lin Zhaopei Guo Jie Chen Atsushi Maruyama Huayu Tian Xuesi Chen |
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| Institution: | 1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China;2. University of Science and Technology of China, Hefei 230026, China;3. Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China;4. Department of Life Science and Technology, Tokyo Institute of Technology, Nagatsuta, Midori, Yokohama 226-8501, Japan |
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| Abstract: | Despite of the promising achievements of immune checkpoints blockade therapy (ICB) in the clinic, which was often limited by low objective responses and severe side effects. Herein, we explored a synergistic strategy to combine in situ vaccination and gene-mediated anti-PD therapy, which was generated by unmethylated cytosine-phosphate-guanine (CpG) and pshPD-L1 gene co-delivery. PEI worked as the delivery carrier to co-deliver the CpG and pshPD-L1 genes, the formed PDC (PEI/DNA/CpG) nanoparticles were further shielded by aldehyde modified polyethylene glycol (OHC-PEG-CHO) via pH responsive Schiff base reaction for OHC-PEG-CHO-PEI/DNA/CpG nanoparticles (P(PDC) NPs) preparation. All steps could be finished within 30 min. Such simple nanoparticles achieved the synergistic antitumor efficacy in B16F10 tumor-bearing mice, and the amplified T cell responses, together with enhanced NK cells infiltration were observed after the combined treatments. In addition, the pH responsive delivery system reduced the side effects triggered by anti-PD therapy. The facile and effective combination strategy we presented here might provide a novel treatment for tumor inhibition. |
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| Keywords: | CpG PD-L1 Immunotherapy Gene therapy |
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