Engineered CD8+ T cell-derived extracellular vesicles induce enhanced anti-cancer efficacy and targeting to lung cancer cells

Hanchae Cho, Inseong Jung, Hyunji Ju, Moon Chang Baek, Kyungmoo Yea

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Lung cancer is a common and highly malignant tumor. Although lung cancer treatments continue to advance, conventional therapies are limited and the response rate of patients to immuno-oncology drugs is low. This phenomenon raises an urgent need to develop effective therapeutic strategies for lung cancer. In this study, we genetically modified human primary CD8+ T cells and obtained antitumor extracellular vesicles (EVs) from them. The engineered EVs, containing interlekin-2 and the anti-epidermal growth factor receptor (EGFR) antibody cetuximab on their surfaces, exhibited direct cytotoxicity against A549 human lung cancer cells and increased cancer cell susceptibility to human peripheral blood mononuclear cell-mediated cytotoxicity. In addition, the engineered EVs specifically targeted the lung cancer cells in an EGFR-dependent manner. Taken together, these findings show that surface engineering of cytokines and antibodies on CD8+ T cell-derived EVs not only enhances their antitumor effects but also confers target specificity, suggesting a potential of modifying the immune cell-derived EVs in cancer treatment.

Original languageEnglish
Article number156249
JournalCytokine
Volume169
DOIs
StatePublished - Sep 2023

Keywords

  • Cetuximab
  • Cytotoxic T cell
  • Extracellular vesicles
  • Interleukin-2
  • Lung cancer

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