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T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation.
- Source :
-
Blood . 8/30/2012, Vol. 120 Issue 9, p1820-1830. 11p. - Publication Year :
- 2012
-
Abstract
- The genetic modification of T cells with a suicide gene grants a mechanism of control of adverse reactions, allowing safe infusion after partially incompatible hematopoietic stem cell transplantation (HSCT). In the TK007 clinical trial, 22 adults with hematologic malignancies experienced a rapid and sustained immune recovery after T cell–depleted HSCT and serial infusions of purified donor T cells expressing the HSV thymidine kinase suicide gene (TK+ cells). After a first wave of circulating TK+ cells, the majority of T cells supporting long-term immune reconstitution did not carry the suicide gene and displayed high numbers of naive lymphocytes, suggesting the thymus-dependent development of T cells, occurring only upon TK+-cell engraftment. Accordingly, after the infusions, we documented an increase in circulating TCR excision circles and CD31+ recent thymic emigrants and a substantial expansion of the active thymic tissue as shown by chest tomography scans. Interestingly, a peak in the serum level of IL-7 was observed after each infusion of TK+ cells, anticipating the appearance of newly generated T cells. The results of the present study show that the infusion of genetically modified donor T cells after HSCT can drive the recovery of thymic activity in adults, leading to immune reconstitution. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00064971
- Volume :
- 120
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 79929403
- Full Text :
- https://doi.org/10.1182/blood-2012-01-405670