title: Recombinant human interleukin-7 (CYT107) promotes T-cell recovery after allogeneic stem cell transplantation.
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).
authors.affiliation: Adult Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. peralesm@mskcc.org
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.forename: Jenna D
authors.initials: JD
authors.lastname: Goldberg
authors.forename: Jianda
authors.initials: J
authors.lastname: Yuan
authors.forename: Guenther
authors.initials: G
authors.lastname: Koehne
authors.forename: Lauren
authors.initials: L
authors.lastname: Lechner
authors.forename: Esperanza B
authors.initials: EB
authors.lastname: Papadopoulos
authors.forename: James W
authors.initials: JW
authors.lastname: Young
authors.forename: Ann A
authors.initials: AA
authors.lastname: Jakubowski
authors.forename: Bushra
authors.initials: B
authors.lastname: Zaidi
authors.forename: Humilidad
authors.initials: H
authors.lastname: Gallardo
authors.forename: Cailian
authors.initials: C
authors.lastname: Liu
authors.forename: Teresa
authors.initials: T
authors.lastname: Rasalan
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.forename: Therese
authors.initials: T
authors.lastname: Croughs
authors.forename: Michel
authors.initials: M
authors.lastname: Morre
authors.forename: Sean M
authors.initials: SM
authors.lastname: Devlin
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006086:Graft vs Host Disease / Q000139:chemically induced; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins