1. T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation.
- Author
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Vago, Luca, Olivelra, Giacomo, Bondanza, Attilio, Noviello, Maddalena, Soldati, Corrado, Ghio, Domenico, Brigida, Immacolata, Greco, Raffaella, Lupo Stanghellini, Maria Teresa, Peccatori, Jacopo, Fracchia, Sergio, Del Fiacco, Matteo, Traversari, Gatia, Aiuti, Alessandro, Del Maschio, Alessandro, Bordignon, Claudio, Giceri, Fablo, and Bonini, Chiara
- Subjects
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T cells , *GENE therapy , *HEMATOPOIETIC stem cell transplantation , *CLINICAL trials , *HEMATOLOGIC malignancies , *TOMOGRAPHY - 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]
- Published
- 2012
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