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Curvature-sensing peptide inhibits tumour-derived exosomes for enhanced cancer immunotherapy

Sol Shin1, Hyewon Ko2,3, Chan Ho Kim4

  • 1Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.

Nature Materials
|March 24, 2023
PubMed

Insights

Engineered peptides disrupt tumour-derived exosomes (T-EXOs), enhancing cancer immunotherapy. This approach reduces immune suppression and improves T-cell function, offering a new strategy against cancer.

Area of Science:

  • Oncology
  • Immunology
  • Biotechnology

Background:

  • Tumour-derived exosomes (T-EXOs) hinder immune checkpoint blockade therapies.
  • Pharmacological inhibition of T-EXOs is a key goal for cancer treatment.

Purpose of the Study:

  • To develop a peptide-based strategy to disrupt T-EXOs for enhanced cancer immunotherapy.
  • To investigate the efficacy of a repurposed antiviral peptide in combination with immune checkpoint blockade.

Main Methods:

  • Engineering an antiviral peptide with membrane-disrupting properties targeting T-EXOs.
  • Testing the peptide's inhibitory effects on T-EXOs from various cancer types.
  • Evaluating the combination therapy in tumour-bearing mice models.

Main Results:

  • The engineered peptide effectively disrupts T-EXOs across different cancer types.
  • pH-enhanced membrane disruption of T-EXOs was observed, relevant to the tumour microenvironment.
  • Combination therapy improved treatment outcomes, reduced exosomal PD-L1, restored T-cell function, and reshaped the tumour microenvironment.

Conclusions:

  • Peptide-induced T-EXO depletion is a viable strategy to enhance cancer immunotherapy.
  • Peptide engineering offers a promising avenue for exosome-targeting applications in cancer treatment.

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