期刊
BLOOD
卷 120, 期 24, 页码 4882-4891出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-06-437236
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资金
- National Institutes of Health [P01 CA23766, R01-HL069929, R01-CA107096, R01-AI080455]
- US Department of Defense [W81XWH-09-1-0294]
- Radiation Effects Research Foundation (RERF-NIAID)
- Translational and Integrative Medicine Research Fund of Memorial Sloan-Kettering Cancer Center
- Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center
- Mr William H. Goodwin and Mrs Alice Goodwin
- Cycle for Survival
- New York Community Trust
- When Everyone Survives
- Lymphoma Foundation
- Leukemia & Lymphoma Society
- Alex's Lemonade Stand
- Geoffrey Beene Cancer Research Center at Memorial Sloan-Kettering Cancer Center
- Peter Solomon Fund
- Cytheris Inc
- Cytheris S.A.
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). (Blood. 2012;120(24):4882-4891)
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