Rapid single-cell identification of Epstein-Barr virus-specific T-cell receptors for cellular therapy.
Cytotherapy
; 24(8): 818-826, 2022 08.
Article
en En
| MEDLINE
| ID: mdl-35525797
ABSTRACT
BACKGROUND AND AIMS:
Epstein-Barr virus (EBV) is associated with solid and hematopoietic malignancies. After allogeneic stem cell transplantation, EBV infection or reactivation represents a potentially life-threatening condition with no specific treatment available in clinical routine. In vitro expansion of naturally occurring EBV-specific T cells for adoptive transfer is time-consuming and influenced by the donor's T-cell receptor (TCR) repertoire and requires a specific memory compartment that is non-existent in seronegative individuals. The authors present highly efficient identification of EBV-specific TCRs that can be expressed on human T cells and recognize EBV-infected cells. METHODS ANDRESULTS:
Mononuclear cells from six stem cell grafts were expanded in vitro with three HLA-B*3501- or four HLA-A*0201-presented peptides derived from six EBV proteins expressed during latent and lytic infection. Epitope-specific T cells expanded on average 42-fold and were single-cell-sorted and TCRαß-sequenced. To confirm specificity, 11 HLA-B*3501- and six HLA-A*0201-restricted dominant TCRs were expressed on reporter cell lines, and 16 of 17 TCRs recognized their presumed target peptides. To confirm recognition of virus-infected cells and assess their value for adoptive therapy, three selected HLA-B*3501- and four HLA-A*0201-restricted TCRs were expressed on human peripheral blood lymphocytes. All TCR-transduced cells recognized EBV-infected lymphoblastoid cell lines.CONCLUSIONS:
The authors' approach provides sets of EBV epitope-specific TCRs in two different HLA contexts. Resulting cellular products do not require EBV-seropositive donors, can be adjusted to cell subsets of choice with exactly defined proportions of target-specific T cells, can be tracked in vivo and will help to overcome unmet clinical needs in the treatment and prophylaxis of EBV reactivation and associated malignancies.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Herpesvirus Humano 4
/
Infecciones por Virus de Epstein-Barr
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cytotherapy
Asunto de la revista:
TERAPEUTICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania