Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches
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 effic...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2024.2432345 |
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| author | Daouda Abba Moussa Mario Vazquez Christine Chable-Bessia Vincent Roux-Portalez Elia Tamagnini Mattia Pedotti Luca Simonelli Giang Ngo Manon Souchard Sebastien Lyonnais Myriam Chentouf Nathalie Gros Soledad Marsile-Medun Heiko Dinter Martine Pugnière Pierre Martineau Luca Varani Manel Juan Hugo Calderon Mar Naranjo-Gomez Mireia Pelegrin |
| author_facet | Daouda Abba Moussa Mario Vazquez Christine Chable-Bessia Vincent Roux-Portalez Elia Tamagnini Mattia Pedotti Luca Simonelli Giang Ngo Manon Souchard Sebastien Lyonnais Myriam Chentouf Nathalie Gros Soledad Marsile-Medun Heiko Dinter Martine Pugnière Pierre Martineau Luca Varani Manel Juan Hugo Calderon Mar Naranjo-Gomez Mireia Pelegrin |
| author_sort | Daouda Abba Moussa |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-adcce9f585fb4559a8b09e0bfdec259a |
| institution | Kabale University |
| issn | 2222-1751 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-adcce9f585fb4559a8b09e0bfdec259a2024-12-15T17:47:38ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2024.2432345Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approachesDaouda Abba Moussa0Mario Vazquez1Christine Chable-Bessia2Vincent Roux-Portalez3Elia Tamagnini4Mattia Pedotti5Luca Simonelli6Giang Ngo7Manon Souchard8Sebastien Lyonnais9Myriam Chentouf10Nathalie Gros11Soledad Marsile-Medun12Heiko Dinter13Martine Pugnière14Pierre Martineau15Luca Varani16Manel Juan17Hugo Calderon18Mar Naranjo-Gomez19Mireia Pelegrin20IRMB, University of Montpellier, INSERM, CNRS, Montpellier, FranceIDIBAPS, Immunogenetics and Immunotherapy in Autoinflammatory and Immune Responses, Barcelona, SpainCEMIPAI, University of Montpellier, UAR3725 CNRS, Montpellier, FranceIRCM, University of Montpellier, ICM, INSERM, Montpellier, FranceInstitute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, SwitzerlandInstitute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, SwitzerlandInstitute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, SwitzerlandIRCM, University of Montpellier, ICM, INSERM, Montpellier, FranceIRMB, University of Montpellier, INSERM, CNRS, Montpellier, FranceCEMIPAI, University of Montpellier, UAR3725 CNRS, Montpellier, FranceIRCM, University of Montpellier, ICM, INSERM, Montpellier, FranceCEMIPAI, University of Montpellier, UAR3725 CNRS, Montpellier, FranceIRMB, University of Montpellier, INSERM, CNRS, Montpellier, FranceIRMB, University of Montpellier, INSERM, CNRS, Montpellier, FranceIRCM, University of Montpellier, ICM, INSERM, Montpellier, FranceIRCM, University of Montpellier, ICM, INSERM, Montpellier, FranceInstitute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, SwitzerlandIDIBAPS, Immunogenetics and Immunotherapy in Autoinflammatory and Immune Responses, Barcelona, SpainIDIBAPS, Immunogenetics and Immunotherapy in Autoinflammatory and Immune Responses, Barcelona, SpainIRMB, University of Montpellier, INSERM, CNRS, Montpellier, FranceIRMB, University of Montpellier, INSERM, CNRS, Montpellier, FranceUnlocking 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.https://www.tandfonline.com/doi/10.1080/22221751.2024.2432345Non-neutralizing antibodiesinfected cell-targetingSARS-CoV-2antibody-based therapycell therapyCAR-T cells |
| spellingShingle | Daouda Abba Moussa Mario Vazquez Christine Chable-Bessia Vincent Roux-Portalez Elia Tamagnini Mattia Pedotti Luca Simonelli Giang Ngo Manon Souchard Sebastien Lyonnais Myriam Chentouf Nathalie Gros Soledad Marsile-Medun Heiko Dinter Martine Pugnière Pierre Martineau Luca Varani Manel Juan Hugo Calderon Mar Naranjo-Gomez Mireia Pelegrin Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches Emerging Microbes and Infections Non-neutralizing antibodies infected cell-targeting SARS-CoV-2 antibody-based therapy cell therapy CAR-T cells |
| title | Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches |
| title_full | Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches |
| title_fullStr | Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches |
| title_full_unstemmed | Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches |
| title_short | Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches |
| title_sort | discovery of a pan anti sars cov 2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches |
| topic | Non-neutralizing antibodies infected cell-targeting SARS-CoV-2 antibody-based therapy cell therapy CAR-T cells |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2024.2432345 |
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