Abstract
Immune checkpoint inhibitors (ICIs) have emerged as effective cancer therapeutic agents. However, immune-related adverse effects, high treatment costs, and low therapeutic efficacy against rapidly growing tumors limit their clinical applications. Here, we developed thiostrepton-loaded nanoliposomes (ThioLipos) as novel therapeutic drugs to overcome the limitations of ICIs and for enhancing the efficacy of cancer immunotherapy. Thiostrepton, a forkhead box M1 inhibitor, induced a significant reduction in programmed death ligand-1 (PD-L1) levels and viability of human and murine colon cancer cells. The therapeutic potential of ThioLipos in cancer immunotherapy was evaluated using a MC38 syngeneic tumor model. For mice with rapidly growing colon tumors, ThioLipo treatment alone resulted in therapeutic outcomes similar to those of ICI treatment. Moreover, combined therapy with ThioLipos and ICIs (anti-4-1BB or anti-PD-1 antibodies) resulted in synergistic tumor growth inhibition when compared with ThioLipo or ICI treatment alone, and no side effects were observed in normal tissues. These results suggest that ThioLipos can be used as promising nano-immunotherapeutics for overcoming the limitations of ICIs and enhancing the efficacy of cancer immunotherapy.
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