Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches.

Autor:	Moussa DA; IRMB, Université Montpellier, INSERM, CNRS, Montpellier, France., Vazquez M; Department of Immunology, Hospital Clínic de Barcelona, Barcelona, Spain., Chable-Bessia C; CEMIPAI, University of Montpellier, UAR3725 CNRS, Montpellier, France., Roux-Portalez V; IRCM, Univ Montpellier, ICM, INSERM, Montpellier, France.; GenAc, Siric Plateform, INSERM, Montpellier, France., Tamagnini E; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland., Pedotti M; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland., Simonelli L; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland., Ngo G; IRCM, Univ Montpellier, ICM, INSERM, Montpellier, France.; PPM, BioCampus Plateforme de Protéomique de Montpellier CNRS France., Souchard M; IRMB, Université Montpellier, INSERM, CNRS, Montpellier, France., Lyonnais S; CEMIPAI, University of Montpellier, UAR3725 CNRS, Montpellier, France., Chentouf M; IRCM, Univ Montpellier, ICM, INSERM, Montpellier, France.; GenAc, Siric Plateform, INSERM, Montpellier, France., Gros N; CEMIPAI, University of Montpellier, UAR3725 CNRS, Montpellier, France., Marsile-Medun S; IRMB, Université Montpellier, INSERM, CNRS, Montpellier, France., Dinter H; IRMB, Université Montpellier, INSERM, CNRS, Montpellier, France., Pugnière M; IRCM, Univ Montpellier, ICM, INSERM, Montpellier, France.; PPM, BioCampus Plateforme de Protéomique de Montpellier CNRS France., Martineau P; IRCM, Univ Montpellier, ICM, INSERM, Montpellier, France.; GenAc, Siric Plateform, INSERM, Montpellier, France., Varani L; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland., Juan M; Department of Immunology, Hospital Clínic de Barcelona, Barcelona, Spain., Calderon H; Department of Immunology, Hospital Clínic de Barcelona, Barcelona, Spain., Naranjo-Gomez M; IRMB, Université Montpellier, INSERM, CNRS, Montpellier, France., Pelegrin M; IRMB, Université Montpellier, INSERM, CNRS, Montpellier, France.
Jazyk:	angličtina
Zdroj:	Emerging microbes & infections [Emerg Microbes Infect] 2024 Nov 25, pp. 2432345. Date of Electronic Publication: 2024 Nov 25.
DOI:	10.1080/22221751.2024.2432345
Abstrakt:	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..
Databáze:	MEDLINE
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