Identification and characterization of T-cell receptors with therapeutic potential showing conserved specificity against all SARS-CoV 2 strains

Reimann H, Moosmann C, Schober K, Lang V, Verhagen J, Zeun J, Mackensen A, Kremer A, Völkl S, Aigner M (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Immunobiology Elsevier

Book Volume: 228

Article Number: 152720

Journal Issue: 5

DOI: 10.1016/j.imbio.2023.152720

Abstract

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.

Authors with CRIS profile

Hannah Reimann Department of Medicine 5 – Haematology and Oncology Carolin Moosmann Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Kilian Schober Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Johan Verhagen Department of Medicine 5 – Haematology and Oncology Andreas Mackensen Lehrstuhl für Innere Medizin V Anita Kremer Department of Medicine 5 – Haematology and Oncology Simon Völkl Department of Medicine 5 – Haematology and Oncology

How to cite

APA:

Reimann, H., Moosmann, C., Schober, K., Lang, V., Verhagen, J., Zeun, J.,... Aigner, M. (2023). Identification and characterization of T-cell receptors with therapeutic potential showing conserved specificity against all SARS-CoV 2 strains. Immunobiology, 228(5). https://doi.org/10.1016/j.imbio.2023.152720

MLA:

Reimann, Hannah, et al. "Identification and characterization of T-cell receptors with therapeutic potential showing conserved specificity against all SARS-CoV 2 strains." Immunobiology 228.5 (2023).

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