| Autor: |
Wesley, Huisman, Marthe C J, Roex, Lois, Hageman, Eva A S, Koster, Sabrina A J, Veld, Conny, Hoogstraten, Peter, van Balen, H M Esther, van Egmond, Cornelis A M, Van Bergen, Hermann, Einsele, Lothar, Germeroth, Derk, Amsen, J H Frederik, Falkenburg, Inge, Jedema |
| Rok vydání: |
2022 |
| Zdroj: |
Blood advances. |
| ISSN: |
2473-9537 |
| Popis: |
Adoptive cellular therapies with T cells are increasingly used to treat a variety of conditions. For instance, in a recent phase I/II trial, we prophylactically administered multi-virus-specific T-cell products to protect recipients of T-cell depleted allogeneic stem-cell grafts against viral reactivations. To establish treatment efficacy, it is important to determine the fate of the individual transferred T-cell populations. However, it is difficult to unequivocally distinguish progeny of the transferred T-cell products from recipient- or stem-cell graft-derived T cells that survived T-cell depletion during conditioning or stem-cell graft manipulation. Using mRNA sequencing of the TCRβ-chains of the individual virus-specific T-cell populations within these T-cell products, we were now able to track the multiple clonal virus-specific subpopulations in peripheral blood and distinguish recipient- and stem-cell graft-derived virus-specific T cells from the progeny of the infused T-cell products. We observed in vivo expansion of virus-specific T cells that were exclusively derived from the T-cell products with similar kinetics as the expansion of virus-specific T cells that could also be detected before the T-cell product infusion. Additionally, we demonstrated persistence of virus-specific T cells derived from the T-cell products in most patients who did not show viral reactivations. This study demonstrates that virus-specific T cells from prophylactically infused multi-antigen-specific T-cell products can expand in response to antigen encounter in vivo and even persist in the absence of early viral reactivations. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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