Off-the-Shelf Partial HLA Matching SARS-CoV-2 Antigen Specific T Cell Therapy: A New Possibility for COVID-19 Treatment.
Front Immunol
; 12: 751869, 2021.
Article
in English
| MEDLINE | ID: covidwho-1634057
ABSTRACT
BACKGROUND:
Immunological characteristics of COVID-19 show pathological hyperinflammation associated with lymphopenia and dysfunctional T cell responses. These features provide a rationale for restoring functional T cell immunity in COVID-19 patients by adoptive transfer of SARS-CoV-2 specific T cells.METHODS:
To generate SARS-CoV-2 specific T cells, we isolated peripheral blood mononuclear cells from 7 COVID-19 recovered and 13 unexposed donors. Consequently, we stimulated cells with SARS-CoV-2 peptide mixtures covering spike, membrane and nucleocapsid proteins. Then, we culture expanded cells with IL-2 for 21 days. We assessed immunophenotypes, cytokine profiles, antigen specificity of the final cell products.RESULTS:
Our results show that SARS-CoV-2 specific T cells could be expanded in both COVID-19 recovered and unexposed groups. Immunophenotypes were similar in both groups showing CD4+ T cell dominance, but CD8+ and CD3+CD56+ T cells were also present. Antigen specificity was determined by ELISPOT, intracellular cytokine assay, and cytotoxicity assays. One out of 14 individuals who were previously unexposed to SARS-CoV-2 failed to show antigen specificity. Moreover, ex-vivo expanded SARS-CoV-2 specific T cells mainly consisted of central and effector memory subsets with reduced alloreactivity against HLA-unmatched cells suggesting the possibility for the development of third-party partial HLA-matching products.DISCUSSION:
In conclusion, our findings show that SARS-CoV-2 specific T cell can be readily expanded from both COVID-19 and unexposed individuals and can therefore be manufactured as a biopharmaceutical product to treat severe COVID-19 patients. ONE SENTENCESUMMARY:
Ex-vivo expanded SARS-CoV-2 antigen specific T cells developed as third-party partial HLA-matching products may be a promising approach for treating severe COVID-19 patients that do not respond to previous treatment options.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
CD4-Positive T-Lymphocytes
/
CD8-Positive T-Lymphocytes
/
Adoptive Transfer
/
SARS-CoV-2
/
COVID-19
Type of study:
Experimental Studies
/
Randomized controlled trials
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
/
Young adult
Language:
English
Journal:
Front Immunol
Year:
2021
Document Type:
Article
Affiliation country:
Fimmu.2021.751869
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