4.8 Article

Nanomedicine-mediated ubiquitination inhibition boosts antitumor immune response via activation of dendritic cells

期刊

NANO RESEARCH
卷 14, 期 11, 页码 3900-3906

出版社

TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-021-3312-4

关键词

drug delivery; cancer immunotherapy; ubiquitin activating enzyme (UAE) inhibitor; antigen presentation; dendritic cell (DC) maturation

资金

  1. National Key R&D Program of China [2017YFA0205600]
  2. National Natural Science Foundation of China [31870996, 32071378]
  3. Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110102001]
  4. Program for Guangdong Introducing Innovative and Entrepreneurial Teams [2017ZT07S054]
  5. Guangdong Provincial Pearl River Talents Program [2017GC010482]
  6. Guangdong Basic and Applied Basic Research Foundation [2020A1515011297]
  7. Natural Science Foundation of Guangdong Province, China [2019A1515011926]
  8. China Postdoctoral Science Foundation [2018M643096]
  9. Fundamental Research Funds for the Central Universities

向作者/读者索取更多资源

This study developed an effective immunotherapy strategy to improve tumor treatment by enhancing the maturation of DCs and antigen presentation, leading to improved efficacy against poorly immunogenic tumors.
Tumor immunotherapy as a promising method for tumor treatment received tremendous attention. However, the problem of low clinical response rate still needs to be solved, especially in the poorly immunogenic tumors. The enhancement of tumor antigens presentation can effectively activate dendritic cells (DCs) and improve the tumor immunotherapy. In this work, TAK-243 as an inhibitor of the ubiquitin activating enzyme (UAE), was fabricated into cationic lipid-assisted nanoparticle (CLAN(TAK-243)). The obtained CLAN(TAK-243) could act as an effective tumor immunotherapy enhancer to promote the maturation of DCs as well as antigen presentation, which obviously stimulated the T cells activation and proliferation. Such CLAN(TAK-243) injected intravenously could well trigger immune response to tumor cells in vivo. Importantly, mice treated with CLAN(TAK-243) could obtain a long immune memory effect to protect themselves from re-challenged tumor cells. Therefore, this work presented an effective immunotherapy strategy for poorly immunogenic tumor.

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