Résumé
derivatives offers a therapeutic avenue against severe COVID-19, especially crucial for safeguarding high-risk populations. Novel mAb-based immunotherapies may help address the reduced efficacy of current vaccines and neutralizing mAbs caused by the emergence of variants of concern (VOC). Using phage display technology, we discovered a pan-SARS-CoV-2 mAb (C10 mAb) that targets a conserved region of SARS-CoV-2 and demonstrates exceptional efficacy in recognizing all assessed VOC strains, including the latest Omicron variants. While C10 lacks direct neutralization capacity, its proficiency in binding infected cells and inducing the lysis of lung epithelial cells via antibody-dependent cellular cytotoxicity (ADCC) highlights the significance of the potential use of non-neutralizing mAbs in the battle against infection. Building upon this pan-SARS-CoV-2 mAb, we engineered C10-based CAR-T cells endowed with efficient killing capacity against SARS-CoV-2-infected lung epithelial cells. Notably, C10-based CAR-T cells exhibit robust proliferation capacity and reduced expression of exhaustion cell surface markers. Our study unveils a pan-SARS-CoV-2 mAb effective in targeting infected cells and offers a proof-of-concept for the potential application of CAR-T cell therapy in combatting SARS-CoV-2 infections. Furthermore, it holds promise for the development of innovating antibody-based and cell-based therapeutic strategies against severe COVID-19 by expanding the array of therapeutic options available for high-risk populations.