Developing CAR-immune cell therapy against SARS-CoV-2: Current status, challenges and prospects

Chen, Yizhao; Liu, Chong; Fang, Yilong; Chen, Weile; Qiu, Jiaqi; Zhu, Mengjuan; Wei, Wei; Tu, Jiajie

doi:10.1016/j.bcp.2024.116066

Biochemical Pharmacology

2024

DOI: 10.1016/j.bcp.2024.116066

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Developing CAR-immune cell therapy against SARS-CoV-2: Current status, challenges and prospects

Yizhao Chen,

Chong Liu,

Yilong Fang

et al.

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Cited by 2 publications

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CAR-T therapy for ovarian cancer: Recent advances and future directions

Xin,

Chen,

Sun

et al. 2024

Biochemical Pharmacology

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CAR-T therapy for ovarian cancer: Recent advances and future directions

Xin,

Chen,

Sun

et al. 2024

Biochemical Pharmacology

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

Abba Moussa,

Vazquez,

Chable-Bessia

et al. 2024

Emerging Microbes & Infections

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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:

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Developing CAR-immune cell therapy against SARS-CoV-2: Current status, challenges and prospects

Cited by 2 publications

References 101 publications

CAR-T therapy for ovarian cancer: Recent advances and future directions

CAR-T therapy for ovarian cancer: Recent advances and future directions

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

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