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Updated: Jul 20, 2025
Detection of SARS-CoV-2 Receptor-Binding Domain Antibody using a HiBiT-Based Bioreporter
Published on: August 12, 2021
Identification and characterization of T-cell receptors with therapeutic potential showing conserved specificity
Hannah Reimann1, Carolin Moosmann2, Kilian Schober3
1Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany; Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany.
Introduction:
Treatment of severe COVID-19 disease can be challenging in immunocompromized patients due to newly emerging virus variants of concern (VOC) escaping the humoral response. Thus, T cells recognizing to date unmutated epitopes are not only relevant for patients' immune responses against VOC, but might also serve as a therapeutic option for patients with severe COVID-19 disease in the future, e.g. following allogenic stem cell transplantation.
Methods:
To this purpose, the activation, cytokine profile and specificity of T-cell clones against unmutated and omicron Spike (S)-protein was analyzed, HLA restriction was determined and most promising T-cell receptor (TCR) was introduced into allogeneic T cells via CRISPR/Cas9-mediated orthotopic TCR replacement. Finally, T-cell responses of engineered T cells was determined and durability of the TCR replacement measured.
Perspective:
SARS-CoV-2 specific engineered T cells recognizing a genomically stable region of the S-protein of all SARS-CoV 2 variants were successfully generated. Such transgenic T cells exhibit favorable effector functions and provide a treatment option of immunocompromised COVID-19 patients.
Insights
Engineered T cells targeting conserved regions of SARS-CoV-2 offer a potential therapy for immunocompromised patients. These T cells recognize all variants, providing a durable immune response against COVID-19.
Area of Science:
- Immunology
- Virology
- Biotechnology
Background:
- Severe COVID-19 in immunocompromised patients is challenging due to viral variants evading immune responses.
- T cells recognizing unmutated viral epitopes are crucial for combating variants of concern (VOC).
Purpose of the Study:
- To develop a T-cell based therapy for immunocompromised COVID-19 patients.
- To engineer T cells targeting conserved regions of the SARS-CoV-2 Spike protein.
Main Methods:
- Analysis of T-cell activation, cytokine profiles, and specificity against SARS-CoV-2 Spike protein variants.
- CRISPR/Cas9-mediated orthotopic T-cell receptor (TCR) replacement in allogeneic T cells.
- Assessment of engineered T-cell function and durability.
Main Results:
- Successfully generated SARS-CoV-2 specific engineered T cells recognizing a stable region of the Spike protein.
- Engineered T cells demonstrated favorable effector functions.
- Transgenic T cells recognized all SARS-CoV-2 variants, including Omicron.
Conclusions:
- Engineered T cells provide a potential therapeutic strategy for immunocompromised COVID-19 patients.
- This approach offers a durable treatment option against current and future SARS-CoV-2 variants.
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