Recombinant human interleukin-7 (CYT107) promotes T-cell recovery after allogeneic stem cell transplantation

• Published in: Blood Vol. 120; no. 24; pp. 4882 - 4891
• Main Authors: Perales, Miguel-Angel, Goldberg, Jenna D., Yuan, Jianda, Koehne, Guenther, Lechner, Lauren, Papadopoulos, Esperanza B., Young, James W., Jakubowski, Ann A., Zaidi, Bushra, Gallardo, Humilidad, Liu, Cailian, Rasalan, Teresa, Wolchok, Jedd D., Croughs, Therese, Morre, Michel, Devlin, Sean M., van den Brink, Marcel R.M.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 06-12-2012; Americain Society of Hematology; American Society of Hematology
• Subjects: Adult; Aged; Area Under Curve; Biological and medical sciences; 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; Clinical Trials and Observations; Combined Modality Therapy; Dose-Response Relationship, Drug; Female; Gene Rearrangement, T-Lymphocyte; Graft vs Host Disease - chemically induced; Hematologic and hematopoietic diseases; Hematologic Neoplasms - immunology; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation - methods; Humans; Interleukin-7 - genetics; Interleukin-7 - pharmacokinetics; Interleukin-7 - therapeutic use; Interleukin-7 Receptor alpha Subunit - immunology; Interleukin-7 Receptor alpha Subunit - metabolism; Male; Medical sciences; 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 - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transplantation; Transplantation, Homologous; Treatment Outcome; Human; Interleukin 7; Allogeneic hematopoietic stem cell transplantation; Hematology; Stem cell; Cytokine; Hematopoietic cell; Homograft; Immune reconstitution; Graft; Recombinant protein
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2012-06-437236

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).