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Recombinant human interleukin-7 (CYT107) promotes T-cell recovery after allogeneic stem cell transplantation.
- Source :
-
Blood [Blood] 2012 Dec 06; Vol. 120 (24), pp. 4882-91. Date of Electronic Publication: 2012 Sep 25. - Publication Year :
- 2012
-
Abstract
- Delays in immune recovery after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with increased risks of infection and relapse. IL-7 has a central role in T-cell development and survival and enhances immune recovery in murine models of allo-HSCT. We performed a phase 1 trial of r-hIL-7 (CYT107) in recipients of T-cell depleted allo-HSCTs. Twelve patients were treated with escalating doses of r-hIL-7 administered weekly for 3 weeks. The study drug was well tolerated with only one patient developing acute skin GVHD. At baseline, patients were profoundly lymphopenic. CYT107 induced a doubling in CD4(+) and CD8(+) T cells. The main effect of IL-7 was an expansion of effector memory T cells, the predominant subset identified in our patients. There was no significant effect on CD4(+)CD25(+)FoxP3(+) T cells, NK, or B cells. Importantly, we not only saw quantitative increases in T cells after a short course of IL-7 but also demonstrated an increase in functional T cells, including viral-specific T cells that recognize CMV. Enhanced TCR diversity was also observed after treatment. Our results indicate that r-hIL-7 can enhance immune recovery after a T cell-depleted allo-HSCT without causing significant GVHD or other serious toxicity (www.clinicaltrials.gov; NCT00684008).
- Subjects :
- Adult
Aged
Area Under Curve
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Cell Proliferation
Combined Modality Therapy
Dose-Response Relationship, Drug
Female
Gene Rearrangement, T-Lymphocyte
Graft vs Host Disease chemically induced
Hematologic Neoplasms immunology
Humans
Interleukin-7 genetics
Interleukin-7 pharmacokinetics
Interleukin-7 Receptor alpha Subunit immunology
Interleukin-7 Receptor alpha Subunit metabolism
Male
Metabolic Clearance Rate
Middle Aged
Receptors, Antigen, T-Cell genetics
Receptors, Antigen, T-Cell immunology
Receptors, Antigen, T-Cell metabolism
Recombinant Proteins adverse effects
Recombinant Proteins pharmacokinetics
Recombinant Proteins therapeutic use
T-Lymphocytes immunology
T-Lymphocytes metabolism
Transplantation, Homologous
Treatment Outcome
Hematologic Neoplasms therapy
Hematopoietic Stem Cell Transplantation methods
Interleukin-7 therapeutic use
T-Lymphocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 120
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 23012326
- Full Text :
- https://doi.org/10.1182/blood-2012-06-437236