Publication Date
7-1-2023
Journal
Haematologica
DOI
10.3324/haematol.2022.281946
PMID
36373249
PMCID
PMC10316279
PubMedCentral® Posted Date
11-10-2022
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
yes
Keywords
Humans, COVID-19, Hematopoietic Stem Cell Transplantation, Lymphocytes, SARS-CoV-2
Abstract
Defects in T-cell immunity to SARS-CoV-2 have been linked to an increased risk of severe COVID-19 (even after vaccination), persistent viral shedding and the emergence of more virulent viral variants. To address this T-cell deficit, we sought to prepare and cryopreserve banks of virus-specific T cells, which would be available as a partially HLA-matched, off-the-shelf product for immediate therapeutic use. By interrogating the peripheral blood of healthy convalescent donors, we identified immunodominant and protective T-cell target antigens, and generated and characterized polyclonal virus-specific T-cell lines with activity against multiple clinically important SARS-CoV-2 variants (including 'delta' and 'omicron'). The feasibility of making and safely utilizing such virus-specific T cells clinically was assessed by administering partially HLA-matched, third-party, cryopreserved SARS-CoV-2-specific T cells (ALVR109) in combination with other antiviral agents to four individuals who were hospitalized with COVID-19. This study establishes the feasibility of preparing and delivering off-the-shelf, SARS-CoV-2-directed, virus-specific T cells to patients with COVID-19 and supports the clinical use of these products outside of the profoundly immune compromised setting.
Included in
Clinical Epidemiology Commons, COVID-19 Commons, Internal Medicine Commons, Medical Sciences Commons
Comments
ClinicalTrials.gov number, NCT04401410)
Associated Data