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.
| Original language | English |
|---|---|
| Pages (from-to) | 1820-1830 |
| Number of pages | 11 |
| Journal | Blood |
| Volume | 120 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Aug 30 2012 |
Fingerprint
ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation. / Vago, Luca; Oliveira, 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, Catia; Aiuti, Alessandro; Del Maschio, Alessandro; Bordignon, Claudio; Ciceri, Fabio; Bonini, Chiara.
In: Blood, Vol. 120, No. 9, 30.08.2012, p. 1820-1830.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation
AU - Vago, Luca
AU - Oliveira, Giacomo
AU - Bondanza, Attilio
AU - Noviello, Maddalena
AU - Soldati, Corrado
AU - Ghio, Domenico
AU - Brigida, Immacolata
AU - Greco, Raffaella
AU - Lupo Stanghellini, Maria Teresa
AU - Peccatori, Jacopo
AU - Fracchia, Sergio
AU - Del Fiacco, Matteo
AU - Traversari, Catia
AU - Aiuti, Alessandro
AU - Del Maschio, Alessandro
AU - Bordignon, Claudio
AU - Ciceri, Fabio
AU - Bonini, Chiara
PY - 2012/8/30
Y1 - 2012/8/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84865708450&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865708450&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-01-405670
DO - 10.1182/blood-2012-01-405670
M3 - Article
C2 - 22709689
AN - SCOPUS:84865708450
VL - 120
SP - 1820
EP - 1830
JO - Blood
JF - Blood
SN - 0006-4971
IS - 9
ER -