Citation: Yingying Hu, Lin Lin, Zhaopei Guo, Jie Chen, Atsushi Maruyama, Huayu Tian, Xuesi Chen. In situ vaccination and gene-medeiated PD-L1 blockade for enhanced tumor immunotherapy[J]. Chinese Chemical Letters, ;2021, 32(5): 1770-1774. doi: 10.1016/j.cclet.2020.12.055 shu

In situ vaccination and gene-medeiated PD-L1 blockade for enhanced tumor immunotherapy

Yingying Hu ^{a, b, c} ,
Lin Lin ^{a, b, c} ,
Zhaopei Guo ^{a, c} ,
Jie Chen ^{a, b, c, *,} ,
Atsushi Maruyama ^d ,
Huayu Tian ^{a, b, c, *,} ,
Xuesi Chen ^{a, b, c}

a.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
b.
University of Science and Technology of China, Hefei 230026, China
c.
Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
d.
Department of Life Science and Technology, Tokyo Institute of Technology, Nagatsuta, Midori, Yokohama 226-8501, Japan

chenjie@ciac.ac.cn

thy@ciac.ac.cn

Received Date: 16 August 2020
Revised Date: 24 December 2020
Accepted Date: 29 December 2020
Available Online: 5 January 2021

Figures(7)

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.
- In situ vaccination,
- CpG,
- PD-L1,
- Immunotherapy,
- Gene therapy
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