title: Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy.
abstract: OBJECTIVE
  Interleukin-7 (IL-7) has critical and nonredundant roles in T-cell development, hematopoiesis, and postdevelopmental immune functions as a prototypic homeostatic cytokine. Based on a large body of preclinical evidence, it may have multiple therapeutic applications in immunodeficiency states, either physiologic (immunosenescence), pathologic (HIV), or iatrogenic (postchemotherapy and posthematopoietic stem cell transplant), and may have roles in immune reconstitution or enhancement of immunotherapy. We report here on the toxicity and biological activity of recombinant human IL-7 (rhIL-7) in humans.
  
  
  METHODS
  Subjects with incurable malignancy received rhIL-7 subcutaneously every other day for 2 weeks in a phase I interpatient dose escalation study (3, 10, 30, and 60 microg/kg/dose). The objectives were safety and dose-limiting toxicity determination, identification of a range of biologically active doses, and characterization of biological and, possibly, antitumor effects.
  
  
  RESULTS
  Mild to moderate constitutional symptoms, reversible spleen and lymph node enlargement, and marked increase in peripheral CD3(+), CD4(+), and CD8(+) lymphocytes were seen in a dose-dependent and age-independent manner in all subjects receiving >or=10 microg/kg/dose, resulting in a rejuvenated circulating T-cell profile, resembling that seen earlier in life. In some subjects, rhIL-7 induced in the bone marrow a marked, transient polyclonal proliferation of pre-B cells showing a spectrum of maturation as well as an increase in circulating transitional B cells.
  
  
  CONCLUSIONS
  This study shows the potent biological activity of rhIL-7 in humans over a well-tolerated dose range and allows further exploration of its possible therapeutic applications.
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-1203, USA. csportes@mail.nih.gov
authors.forename: Claude
authors.initials: C
authors.lastname: Sportès
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Babb
authors.forename: Michael C
authors.initials: MC
authors.lastname: Krumlauf
authors.forename: Frances T
authors.initials: FT
authors.lastname: Hakim
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Chow
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Brown
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Fleisher
authors.forename: Pierre
authors.initials: P
authors.lastname: Noel
authors.forename: Irina
authors.initials: I
authors.lastname: Maric
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: Julie
authors.initials: J
authors.lastname: Engel
authors.forename: Renaud
authors.initials: R
authors.lastname: Buffet
authors.forename: Michel
authors.initials: M
authors.lastname: Morre
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Amato
authors.forename: Andrew
authors.initials: A
authors.lastname: Pecora
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Mackall
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gress
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D017252:CD3 Complex / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D015851:Interleukin-7 / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016879:Salvage Therapy; D055815:Young Adult
chemical_list: D017252:CD3 Complex; C508605:IL7 protein, human; D015851:Interleukin-7; D011994:Recombinant Proteins