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Safety (toxicity), pharmacokinetics, immunogenicity, and impact on elements of the normal immune system of recombinant human IL-15 in rhesus macaques

  1. Author:
    Waldmann, T. A.
    Lugli, E.
    Roederer, M.
    Perera, L. P.
    Smedley, J. V.
    Macallister, R. P.
    Goldman, C. K.
    Bryant, B. R.
    Decker, J. M.
    Fleisher, T. A.
    Lane, H. C.
    Sneller, M. C.
    Kurlander, R. J.
    Kleiner, D. E.
    Pletcher, J. M.
    Figg, W. D.
    Yovandich, J. L.
    Creekmore, S. P.

  2. Author Address

    [Waldmann, TA; Lugli, E; Roederer, M] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA [Waldmann, TA; Perera, LP; Goldman, CK; Bryant, BR; Decker, JM] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA [Smedley, JV; Macallister, RP] SAIC Frederick Inc, Lab Anim Sci Program, Bethesda, MD USA [Fleisher, TA] Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD USA [Lane, HC; Sneller, MC] NIAID, Clin Res Ctr, Bethesda, MD 20892 USA [Kurlander, RJ] Warren G Magnuson Clin Ctr, Hematol Serv Clin Pathol Dept, Bethesda, MD USA [Kleiner, DE] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA [Pletcher, JM] Pathol Associates Inc, Charles River Labs, Frederick, MD USA [Figg, WD] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA [Yovandich, JL; Creekmore, SP] NCI, Biol Resources Branch, Dev Therapeut Program, Frederick, MD 21701 USA;Waldmann, TA (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 10,Rm 4N115,10 Ctr Dr, Bethesda, MD 20892 USA;tawald@helix.nih.gov
    1. Year: 2011
    2. Date: May
  2. Journal: Blood
    1. 117
    2. 18
    3. Pages: 4787-4795
  4. Type of Article: Article
  5. ISSN: 0006-4971
  1. Abstract:

    IL-15 uses the heterotrimeric receptor IL-2/IL-15R beta and the gamma chain shared with IL-2 and the cytokine-specific IL-15R alpha. Although IL-15 shares actions with IL-2 that include activation of natural killer (NK) and CD8 T cells, IL-15 is not associated with capillary leak syndrome, activation-induced cell death, or with a major effect on the number of functional regulatory T cells. To prepare for human trials to determine whether IL-15 is superior to IL-2 in cancer therapy, recombinant human IL-15 (rhIL-15) was produced under current good manufacturing practices. A safety study in rhesus macaques was performed in 4 groups of 6 animals each that received vehicle diluent control or rhIL-15 at 10, 20, or 50 mu g/kg/d IV for 12 days. The major toxicity was grade 3/4 transient neutropenia. Bone marrow examinations demonstrated increased marrow cellularity, including cells of the neutrophil series. Furthermore, neutrophils were observed in sinusoids of enlarged livers and spleens, suggesting that IL-15 mediated neutrophil redistribution from the circulation to tissues. The observation that IL-15 administration was associated with increased numbers of circulating NK and CD8 central and effector-memory T cells, in conjunction with efficacy studies in murine tumor models, supports the use of multiple daily infusions of rhIL-15 in patients with metastatic malignancies. (Blood. 2011; 117(18): 4787-4795)

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External Sources

  1. View Full Text
  2. DOI: 10.1182/blood-2010-10-311456
  3. View record in Web of Science®
  4. WOS: 000290275700020

Library Notes

  1. Fiscal Year: FY2010-2011
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