Materials Today Bio (Jan 2022)

Immunologically modified enzyme-responsive micelles regulate the tumor microenvironment for cancer immunotherapy

  • Zhimin Han,
  • Chunai Gong,
  • Juanjuan Li,
  • Huanhuan Guo,
  • Xinlu Chen,
  • Yangli Jin,
  • Shen Gao,
  • Zongguang Tai

Journal volume & issue
Vol. 13
p. 100170

Abstract

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Immune checkpoint blockade has been proven to have great therapeutic potential and has revolutionized the treatment of tumors. However, various limitations remain, including the low response rate of exhausted T cells and mutual regulation of multiple immunosuppressive cell types that compromise the effect of single-target therapy. Nano-delivery systems can be used to regulate the tumor immune microenvironment in favor of immunotherapy. In this study, we constructed a polypeptide-based micellar system that encapsulates an aryl hydrocarbon receptor (AhR) inhibitor (CH223191) conjugated to T cell activator anti-CD28. The inhibition of AhR activation downregulates the fraction of immunosuppressive cells and effectively inhibits tumor cell metastasis. In addition, the combination with co-stimulatory antibodies improves T-cell activation and synergistically enhances the antitumor effect of AhR inhibitors. The micellar system developed in this study represents a novel and effective tumor immunotherapy approach.

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