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Hydrodynamic Delivery of Human IL-15 cDNA Increases Murine Natural Killer Cell Recovery after Syngeneic Bone Marrow Transplantation

  1. Author:
    Barao, I.
    Alvarez, M.
    Redelman, D.
    Weiss, J. M.
    Ortaldo, J. R.
    Wiltrout, R. H.
    Murphy, W. J.

  2. Author Address

    [Murphy, William J.] Univ Calif Davis, Sch Med, CTSC IRC, Dept Dermatol, Sacramento, CA 95817 USA. [Barao, Isabel] Univ Nevada, Dept Microbiol & Immunol, Reno, NV 89557 USA. [Redelman, Doug] Univ Nevada, Dept Physiol, Reno, NV 89557 USA. [Weiss, Jonathan M.; Ortaldo, John R.; Wiltrout, Robert H.] SAIC Frederick Inc, Natl Canc Inst Frederick, Frederick, MD USA. [Murphy, William J.] Univ Calif Davis, Dept Internal Med, Sacramento, CA 95817 USA.;Murphy, WJ (reprint author), Univ Calif Davis, Sch Med, CTSC IRC, Dept Dermatol, Suite 1630,2921 Stockton Blvd, Sacramento, CA 95817 USA;wmjmurphy@ucdavis.edu
    1. Year: 2011
    2. Date: Dec
  2. Journal: Biology of Blood and Marrow Transplantation
    1. 17
    2. 12
    3. Pages: 1754-1764
  4. Type of Article: Article
  5. ISSN: 1083-8791
  1. Abstract:

    Immune deficiency immediately following bone marrow transplantation (BMT) increases susceptibility to opportunistic infections as well as tumor relapse. Natural Killer (NK) cells play important roles in the resistance to virally infected and transformed cells. Interleukin (IL)-15 has been shown to be essential for NK cell development and survival. We administered human (h) IL-15 cDNA (pIL-15) via hydrodynamic delivery to murine recipients undergoing congenic BMT to determine its effects on NK cell reconstitution. Hydrodynamic pIL-15 delivery resulted in high levels of hIL-15 protein in the serum that lasted for several days and then quickly declined. The appearance of hIL-15 was followed by a significant increase of mature donor-derived NK cells within the bone marrow, spleens, and livers of the treated recipients. No accumulation of immature NK cell progenitors was observed. The NK cells from IL-15-treated recipients displayed an activated phenotype and were lytically active toward tumor targets in vitro to a similar degree as did those cells from recipients treated with control plasmid. This suggests that the predominant effect of IL-15 was a quantitative increase in total NK cell numbers and not qualitative changes in NK cell functions. No toxicities or adverse effects were observed. Studies performed in transplanted mice bearing renal carcinoma tumors demonstrated that this mode of hIL-15 gene delivery resulted in increased antitumor responses. These results support the use of cytokine gene transfer-based regimens as a platform to augment NK cell recovery after BMT. Biol Blood Marrow Transplant 17: 1754-1764 (2011) (C) 2011 American Society for Blood and Marrow Transplantation

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.bbmt.2011.08.023
  3. View record in Web of Science®
  4. WOS: 000300472700006

Library Notes

  1. Fiscal Year: FY2011-2012
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