Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer

• DOI: 10.1186/s12967-023-04206-3
• Publication Date: 2023-06-12T12:02:23Z
• Authors: Wei Zheng; Tianchuan Zhu; Lantian Tang; Zhijian Li; Guanmin Jiang; Xi Huang
• Keywords: Mesothelin

Non-small cell lung cancer (NSCLC) is a worldwide health threat with high annual morbidity and mortality. Chemotherapeutic drugs such as paclitaxel (PTX) have been widely applied clinically. However, systemic toxicity due to the non-specific circulation of PTX often leads multi-organ damage, including liver kidney. Thus, it necessary develop novel strategy enhance targeted antitumor effects PTX.Here, we engineered exosomes derived from T cells expressing chimeric antigen receptor (CAR-Exos), which mesothelin (MSLN)-expressing Lewis (MSLN-LLC) through anti-MSLN single-chain variable fragment (scFv) CAR-Exos. was encapsulated into CAR-Exos (PTX@CAR-Exos) administered via inhalation an orthotopic mouse model.Inhaled PTX@CAR-Exos accumulated within tumor area, reduced size, prolonged survival little toxicity. In addition, reprogrammed microenvironment reversed immunosuppression, attributed infiltrating CD8+ elevated IFN-γ TNF-α levels.Our study provides nanovesicle-based delivery platform promote efficacy chemotherapeutic fewer side effects. This may ameliorate present obstacles clinical treatment cancer.