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

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.

Keywords: Cetuximab; Cytotoxic T cell; Extracellular vesicles; Interleukin-2; Lung cancer.