tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2024 Nov 25:2432345.
doi: 10.1080/22221751.2024.2432345. Online ahead of print. Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches
Daouda Abba Moussa[SUP] 1 [/SUP], Mario Vazquez[SUP] 2 [/SUP], Christine Chable-Bessia[SUP] 3 [/SUP], Vincent Roux-Portalez[SUP] 4 5 [/SUP], Elia Tamagnini[SUP] 6 [/SUP], Mattia Pedotti[SUP] 6 [/SUP], Luca Simonelli[SUP] 6 [/SUP], Giang Ngo[SUP] 4 7 [/SUP], Manon Souchard[SUP] 1 [/SUP], Sebastien Lyonnais[SUP] 3 [/SUP], Myriam Chentouf[SUP] 4 5 [/SUP], Nathalie Gros[SUP] 3 [/SUP], Soledad Marsile-Medun[SUP] 1 [/SUP], Heiko Dinter[SUP] 1 [/SUP], Martine Pugnière[SUP] 4 7 [/SUP], Pierre Martineau[SUP] 4 5 [/SUP], Luca Varani[SUP] 6 [/SUP], Manel Juan[SUP] 2 [/SUP], Hugo Calderon[SUP] 2 [/SUP], Mar Naranjo-Gomez[SUP] 1 [/SUP], Mireia Pelegrin[SUP] 1 [/SUP]
Affiliations
Unlocking the potential of broadly reactive coronavirus monoclonal antibodies (mAbs) and their derivatives offers a transformative 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 (VOCs). Using phage display technology, we discovered a pan-SARS-CoV-2 mAb (C10) that targets a conserved region within the receptor-binding domain (RBD) of the virus. Noteworthy, C10 demonstrates exceptional efficacy in recognizing all assessed VOCs, including recent Omicron variants. While C10 lacks direct neutralization capacity, it efficiently binds to infected lung epithelial cells and induces their lysis via natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Building upon this pan-SARS-CoV-2 mAb, we engineered C10-based, Chimeric Antigen Receptor (CAR)-T cells endowed with efficient killing capacity against SARS-CoV-2-infected lung epithelial cells. Notably, NK and CAR-T-cell mediated killing of lung infected cells effectively reduces viral titers. These findings highlight the potential of non-neutralizing mAbs in providing immune protection against emerging infectious diseases. Our work reveals a pan-SARS-CoV-2 mAb effective in targeting infected cells and demonstrates the proof-of-concept for the potential application of CAR-T cell therapy in combating SARS-CoV-2 infections. Furthermore, it holds promise for the development of innovative antibody-based and cell-based therapeutic strategies against severe COVID-19 by expanding the array of therapeutic options available for high-risk populations.Trial registration: ClinicalTrials.gov identifier: NCT04093596..
Keywords: CAR-T cells; Non-neutralizing antibodies; SARS-CoV-2; antibody-based therapy; cell therapy; infected cell-targeting.
. 2024 Nov 25:2432345.
doi: 10.1080/22221751.2024.2432345. Online ahead of print. Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches
Daouda Abba Moussa[SUP] 1 [/SUP], Mario Vazquez[SUP] 2 [/SUP], Christine Chable-Bessia[SUP] 3 [/SUP], Vincent Roux-Portalez[SUP] 4 5 [/SUP], Elia Tamagnini[SUP] 6 [/SUP], Mattia Pedotti[SUP] 6 [/SUP], Luca Simonelli[SUP] 6 [/SUP], Giang Ngo[SUP] 4 7 [/SUP], Manon Souchard[SUP] 1 [/SUP], Sebastien Lyonnais[SUP] 3 [/SUP], Myriam Chentouf[SUP] 4 5 [/SUP], Nathalie Gros[SUP] 3 [/SUP], Soledad Marsile-Medun[SUP] 1 [/SUP], Heiko Dinter[SUP] 1 [/SUP], Martine Pugnière[SUP] 4 7 [/SUP], Pierre Martineau[SUP] 4 5 [/SUP], Luca Varani[SUP] 6 [/SUP], Manel Juan[SUP] 2 [/SUP], Hugo Calderon[SUP] 2 [/SUP], Mar Naranjo-Gomez[SUP] 1 [/SUP], Mireia Pelegrin[SUP] 1 [/SUP]
Affiliations
- PMID: 39584380
- DOI: 10.1080/22221751.2024.2432345
Unlocking the potential of broadly reactive coronavirus monoclonal antibodies (mAbs) and their derivatives offers a transformative 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 (VOCs). Using phage display technology, we discovered a pan-SARS-CoV-2 mAb (C10) that targets a conserved region within the receptor-binding domain (RBD) of the virus. Noteworthy, C10 demonstrates exceptional efficacy in recognizing all assessed VOCs, including recent Omicron variants. While C10 lacks direct neutralization capacity, it efficiently binds to infected lung epithelial cells and induces their lysis via natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Building upon this pan-SARS-CoV-2 mAb, we engineered C10-based, Chimeric Antigen Receptor (CAR)-T cells endowed with efficient killing capacity against SARS-CoV-2-infected lung epithelial cells. Notably, NK and CAR-T-cell mediated killing of lung infected cells effectively reduces viral titers. These findings highlight the potential of non-neutralizing mAbs in providing immune protection against emerging infectious diseases. Our work reveals a pan-SARS-CoV-2 mAb effective in targeting infected cells and demonstrates the proof-of-concept for the potential application of CAR-T cell therapy in combating SARS-CoV-2 infections. Furthermore, it holds promise for the development of innovative antibody-based and cell-based therapeutic strategies against severe COVID-19 by expanding the array of therapeutic options available for high-risk populations.Trial registration: ClinicalTrials.gov identifier: NCT04093596..
Keywords: CAR-T cells; Non-neutralizing antibodies; SARS-CoV-2; antibody-based therapy; cell therapy; infected cell-targeting.