2. Academic Validation
  3. Curvature-sensing peptide inhibits tumour-derived exosomes for enhanced cancer immunotherapy

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

  • Nat Mater. 2023 May;22(5):656-665. doi: 10.1038/s41563-023-01515-2.
Sol Shin # 1,  Hyewon Ko # 2 3,  Chan Ho Kim 4,  Bo Kyeong Yoon 4 5 6 7,  Soyoung Son 4,  Jae Ah Lee 4,  Jung Min Shin 8,  Jeongjin Lee 1,  Seok Ho Song 4,  Joshua A Jackman 9 10 11,  Jae Hyung Park 12 13 14
Affiliations

Affiliations

  • 1 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
  • 2 Bionanotechnology Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea.
  • 3 School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
  • 4 School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
  • 5 Translational Nanobioscience Research Center, Sungkyunkwan University, Suwon, Republic of Korea.
  • 6 Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon, Republic of Korea.
  • 7 School of Healthcare and Biomedical Engineering, Chonnam National University, Yeosu, Republic of Korea.
  • 8 Division of Biotechnology, Convergence Research Institute, DGIST, Daegu, Republic of Korea.
  • 9 School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon, Republic of Korea. jjackman@skku.edu.
  • 10 Translational Nanobioscience Research Center, Sungkyunkwan University, Suwon, Republic of Korea. jjackman@skku.edu.
  • 11 Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon, Republic of Korea. jjackman@skku.edu.
  • 12 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea. jhpark1@skku.edu.
  • 13 School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon, Republic of Korea. jhpark1@skku.edu.
  • 14 Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon, Republic of Korea. jhpark1@skku.edu.
  • # Contributed equally.
PMID: 36959501 DOI: 10.1038/s41563-023-01515-2
Abstract

Tumour-derived exosomes (T-EXOs) impede Immune Checkpoint blockade therapies, motivating pharmacological efforts to inhibit them. Inspired by how Antiviral curvature-sensing Peptides disrupt membrane-enveloped virus particles in the exosome size range, we devised a broadly useful strategy that repurposes an engineered Antiviral peptide to disrupt membrane-enveloped T-EXOs for synergistic Cancer Immunotherapy. The membrane-targeting peptide inhibits T-EXOs from various Cancer types and exhibits pH-enhanced membrane disruption relevant to the tumour microenvironment. The combination of T-EXO-disrupting peptide and programmed cell death protein-1 antibody-based Immune Checkpoint blockade therapy improves treatment outcomes in tumour-bearing mice. Peptide-mediated disruption of T-EXOs not only reduces levels of circulating exosomal programmed death-ligand 1, but also restores CD8+ T cell effector function, prevents premetastatic niche formation and reshapes the tumour microenvironment in vivo. Our findings demonstrate that peptide-induced T-EXO depletion can enhance Cancer Immunotherapy and support the potential of peptide engineering for exosome-targeting applications.

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