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

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.