Abstract
Adoptive T-cell immunotherapy has provided promising results in the treatment of viral complications in humans, particularly in the context of immunocompromised patients who have exhausted all other clinical options. The capacity to expand T cells from healthy immune individuals is providing a new approach to anti-viral immunotherapy, offering rapid off-the-shelf treatment with tailor-made human leukocyte antigen (HLA)-matched T cells. While most of this research has focused on the treatment of latent viral infections, emerging evidence that SARS-CoV-2-specific T cells play an important role in protection against COVID-19 suggests that the transfer of HLA-matched allogeneic off-the-shelf virus-specific T cells could provide a treatment option for patients with active COVID-19 or at risk of developing COVID-19. We initially screened 60 convalescent individuals and based on HLA typing and T-cell response profile, 12 individuals were selected for the development of a SARS-CoV-2-specific T-cell bank. We demonstrate that these T cells are specific for up to four SARS-CoV-2 antigens presented by a broad range of both HLA class I and class II alleles. These T cells show consistent functional and phenotypic properties, display cytotoxic potential against HLA-matched targets and can recognize HLA-matched cells infected with different SARS-CoV-2 variants. These observations demonstrate a robust approach for the production of SARS-CoV-2-specific T cells and provide the impetus for the development of a T-cell repository for clinical assessment.
Highlights
T-cell immunotherapy is providing a paradigm shift in treatment options for patients with lethal infectious complications [1]
We believe these observations provide critical proof-of-concept that T-cell based immunotherapy may offer an option for the future treatment of immunocompromised patients who remain susceptible to the severe complications associated with COVID-19
While early antiviral T-cell immunotherapy work was pioneered through the use of autologous or hematopoietic stem cell transplant donor peripheral blood mononuclear cells (PBMC) as a source of T cells, more recent approaches have transitioned to the use of cryopreserved T-cell repositories generated from PBMC from allogeneic healthy donors that have defined specificity to the pathogen of choice [6–8]
Summary
In patients with a compromised immune system who are at an increased risk of developing severe COVID-19. Off-the-shelf T-cell immunotherapy is proving to be a powerful tool to treat viral disease in patients with a compromised immune system. We demonstrate that most of the epitopes recognized by these T cells remain unchanged in different variants and that the T cells can recognize cells infected with three different variants of SARS-CoV-2. We believe these observations provide critical proof-of-concept that T-cell based immunotherapy may offer an option for the future treatment of immunocompromised patients who remain susceptible to the severe complications associated with COVID-19
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
