Nanomedicine-mediated ubiquitination inhibition boosts antitumor immune response via activation of dendritic cells
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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 (CLANTAK-243). The obtained CLANTAK-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 CLANTAK-243 injected intravenously could well trigger immune response to tumor cells in vivo. Importantly, mice treated with CLANTAK-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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Nanomedicine-mediated ubiquitination inhibition boosts antitumor immune response via activation of dendritic cells
)
Abstract
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 (CLANTAK-243). The obtained CLANTAK-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 CLANTAK-243 injected intravenously could well trigger immune response to tumor cells in vivo. Importantly, mice treated with CLANTAK-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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Acknowledgements
This work was partially supported by the National Key R & D Program of China (No. 2017YFA0205600), the National Natural Science Foundation of China (Nos. 31870996 and 32071378), Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (No. 2018GZR110102001), the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (No. 2017ZT07S054), Guangdong Provincial Pearl River Talents Program (No. 2017GC010482), Guangdong Basic and Applied Basic Research Foundation (No. 2020A1515011297), the Natural Science Foundation of Guangdong Province, China (No. 2019A1515011926), the China Postdoctoral Science Foundation (No. 2018M643096), and the Fundamental Research Funds for the Central Universities.
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