title: IL-15 administered by continuous infusion to rhesus macaques induces massive expansion of CD8+ T effector memory population in peripheral blood.
abstract: IL-15 promotes activation and maintenance of natural killer (NK) and CD8(+) T effector memory (T(EM)) cells, making it a potential immunotherapeutic agent for the treatment of cancer and immunodeficiency states. Here we report the immunologic effects of 3 different IL-15 dosing strategies in Rhesus macaques. IL-15 at a dose of 20 μg/kg/d administered by continuous intravenous infusion for 10 days resulted in a massive (100-fold) expansion of CD8(+) T(EM) cells in the peripheral blood. In contrast, the administration of 20-40 μg/kg/d of IL-15 by subcutaneous injection resulted in a more modest (10-fold) expansion of CD8(+) T(EM) cells. NK expansion was similar in both the continuous intravenous and daily subcutaneous treatment groups. The observation that IL-15 administered by continuous intravenous infusion is able to induce markedly greater expansions of CD8(+) T(EM) cells than the same dose administered by other routes may have important implications for clinical development of this cytokine.
authors: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. msneller@niaid.nih.gov
authors: Michael C
authors: MC
authors: Sneller
authors: William C
authors: WC
authors: Kopp
authors: Kory J
authors: KJ
authors: Engelke
authors: Jason L
authors: JL
authors: Yovandich
authors: Stephen P
authors: SP
authors: Creekmore
authors: Thomas A
authors: TA
authors: Waldmann
authors: H Clifford
authors: HC
authors: Lane
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects* / Q000276:immunology; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D019409:Interleukin-15 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008253:Macaca mulatta
chemical_list: D019409:Interleukin-15