Immunogenic cell death inducing artificial boron-containing polypeptide development for cancer immunotherapy
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The proteasome is an intracellular organelle that degrades misfolded or ubiquitinated proteins, and mainly involved in the autophagy pathway. However, when proteasome activity is inhibited by a proteasome inhibitor, proteins are accumulated in the cell, causing cytotoxicity. And many boron containing compounds are being made as candidates for proteasome inhibition. Boron compounds inhibit proteasome activity through a reversible interactions with the β-subunits of the 20S proteasome. When proteasome activity is inhibited by boron compounds, endoplasmic reticulum stress is induced, and as result, cell death is induced. In this study, we newly synthesized a boron containing artificial polypeptide for cancer immunotherapy. We confirmed that our polypeptide inhibits the catalytic activity of the proteasome, and induces immunogenic cell death.