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T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation.
- Source :
-
Blood [Blood] 2012 Aug 30; Vol. 120 (9), pp. 1820-30. Date of Electronic Publication: 2012 Jun 18. - 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.
- Subjects :
- Adult
Combined Modality Therapy
Gene Expression
Genes, Transgenic, Suicide genetics
Hematologic Neoplasms blood
Hematologic Neoplasms genetics
Humans
Interleukin-7 blood
Lymphocyte Count
Prospective Studies
Radiography, Thoracic
Regeneration genetics
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes transplantation
Thymidine Kinase genetics
Thymidine Kinase metabolism
Thymus Gland metabolism
Thymus Gland physiopathology
Tomography, X-Ray Computed
Treatment Outcome
Genetic Therapy methods
Hematologic Neoplasms therapy
Hematopoietic Stem Cell Transplantation methods
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 120
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 22709689
- Full Text :
- https://doi.org/10.1182/blood-2012-01-405670