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| Item Type: | Article |
|---|---|
| Title: | Rapid single-cell identification of Epstein-Barr virus-specific T-cell receptors for cellular therapy |
| Creators: |
Lammoglia Cobo, M.F.  ORCID: https://orcid.org/0000-0002-0369-0364, Welters, C. ORCID: https://orcid.org/0000-0002-3098-9003, Rosenberger, L., Leisegang, M. ORCID: https://orcid.org/0000-0003-3692-7142, Dietze, K., Pircher, C., Penter, L. ORCID: https://orcid.org/0000-0002-9060-0207, Gary, R., Bullinger, L. ORCID: https://orcid.org/0000-0002-5890-5510, Takvorian, A., Moosmann, A., Dornmair, K. ORCID: https://orcid.org/0000-0003-0342-5373, Blankenstein, T. ORCID: https://orcid.org/0000-0002-3357-4321, Kammertöns, T. ORCID: https://orcid.org/0000-0003-3309-5141, Gerbitz, A. ORCID: https://orcid.org/0000-0002-0105-2086 and Hansmann, L. ORCID: https://orcid.org/0000-0003-3790-0128
|
| 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 AND RESULTS: Mononuclear cells from six stem cell grafts were expanded in vitro with three HLA-B*35:01- or four HLA-A*02:01-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 TCRαβ-sequenced. To confirm specificity, 11 HLA-B*35:01- and six HLA-A*02:01-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*35:01- and four HLA-A*02:01-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. |
| Keywords: | Adoptive T-Cell Therapy, Allogeneic Stem Cell Transplantation, Epstein-Barr Virus, Single-Cell Technologies, Virus-Associated Malignancies |
| Source: | Cytotherapy |
| ISSN: | 1465-3249 |
| Publisher: | Taylor & Francis |
| Volume: | 24 |
| Number: | 8 |
| Page Range: | 818-826 |
| Date: | August 2022 |
| Official Publication: | https://doi.org/10.1016/j.jcyt.2022.03.005 |
| PubMed: | View item in PubMed |
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