Combining mannose receptor mediated nanovaccines and gene regulated PD-L1 blockade for boosting cancer immunotherapy

Jie Chen; Huapan Fang; Yingying Hu; Jiayan Wu; Sijia Zhang; Yuanji Feng; Lin Lin; Huayu Tian; Xuesi Chen

doi:10.1016/j.bioactmat.2021.05.036

Combining mannose receptor mediated nanovaccines and gene regulated PD-L1 blockade for boosting cancer immunotherapy

Bioact Mater. 2021 Jun 4:7:167-180. doi: 10.1016/j.bioactmat.2021.05.036. eCollection 2022 Jan.

Authors

Jie Chen^{1

2

3}, Huapan Fang^{1

2

4}, Yingying Hu^{1

2}, Jiayan Wu^{1

2}, Sijia Zhang^{1

2}, Yuanji Feng^{1

2}, Lin Lin^{1

2

3}, Huayu Tian^{1

2

3}, Xuesi Chen^{1

2

3}

Affiliations

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 Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, PR China.
⁴ Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for CarbonBased Functional Materials & Devices, Soochow University, Suzhou, 215123, Jiangsu, PR China.

Abstract

Tumor nanovaccines have potential applications in the prevention and treatment of malignant tumors. However, it remains a longstanding challenge in exploiting efficient nanocarriers for inducing potent specifically cellular immune responses. Toward this objective, we herein explore an intensive tumor immunotherapeutic strategy by combining mannosylated nanovaccines and gene regulated PD-L1 blockade for immune stimulation and killing activity. Here, we fabricate a mannose modified PLL-RT (Man-PLL-RT) mediated nanovaccines with dendritic cells (DCs) targeting capacity. Man-PLL-RT is capable of co-encapsulating with antigen (ovalbumin, OVA) and adjuvant (unmethylated cytosine-phosphate-guanine, CpG) by electrostatic interaction. This positively charged Man-PLL-RT/OVA/CpG nanovaccines can facilitate the endocytosis, maturation and cross presentation in DCs. However, the nanovaccines arouse limited inhibition of tumor growth, which is mainly due to the immunosuppressed microenvironment of tumors. Combining tumor nanovaccines with gene regulated PD-L1 blockade leads to an obvious tumor remission in B16F10 melanoma bearing mice. The collaborative strategy provides essential insights to boost the benefits of tumor vaccines by regulating the checkpoint blockade with gene therapy.

Keywords: Gene delivery; Nanovaccines; PD-L1 blockade; Targeted vaccine; Tumor immunotherapy.