Advertisement

Engineering the TGFβ receptor to enhance the therapeutic potential of natural killer cells as an immunotherapy for neuroblastoma

  • Author Footnotes
    * Corresponding author.
    R.A. Burga
    Footnotes
    * Corresponding author.
    Affiliations
    Institute for Biomedical Sciences, George Washington University, Washington, District of Columbia, United States

    Program for Cell Enhancement and Technologies for Innovation, Children's National Health System, Washington, District of Columbia, United States

    GW Cancer Center, George Washington University, Washington, District of Columbia, United States
    Search for articles by this author
  • E. Williams
    Affiliations
    GW Cancer Center, George Washington University, Washington, District of Columbia, United States
    Search for articles by this author
  • E. Yvon
    Affiliations
    GW Cancer Center, George Washington University, Washington, District of Columbia, United States
    Search for articles by this author
  • R. Fernandes
    Affiliations
    Program for Cell Enhancement and Technologies for Innovation, Children's National Health System, Washington, District of Columbia, United States

    GW Cancer Center, George Washington University, Washington, District of Columbia, United States
    Search for articles by this author
  • C.Y. Cruz
    Affiliations
    Institute for Biomedical Sciences, George Washington University, Washington, District of Columbia, United States

    Program for Cell Enhancement and Technologies for Innovation, Children's National Health System, Washington, District of Columbia, United States

    GW Cancer Center, George Washington University, Washington, District of Columbia, United States
    Search for articles by this author
  • C. Bollard
    Affiliations
    Institute for Biomedical Sciences, George Washington University, Washington, District of Columbia, United States

    Program for Cell Enhancement and Technologies for Innovation, Children's National Health System, Washington, District of Columbia, United States

    GW Cancer Center, George Washington University, Washington, District of Columbia, United States
    Search for articles by this author
  • Author Footnotes
    * Corresponding author.
      High-grade neuroblastomas (NB) have a poor prognosis, and there is a need to explore novel therapies. Natural killer (NK) cells rapidly lyse target cells without prior exposure, and serve as a promising source for adoptive cell therapy, however availability from adult donors is limited. Cord blood (CB) derived NK cells have promise as an ideal source for “off the shelf” therapy as they can be selected for optimally mismatched donors. However, CB NK cell efficacy is limited by the immunosuppressive microenvironment in solid tumors such as NB, where high levels of secreted TGFβ actively impairs NK cell activity. To overcome this, we genetically-modified NK cells to express a modified TGFβ receptor which contains an activation domain, and is thus able to engage with TGFβ while potentially converting downstream signals to enhance NK cell function.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Cytotherapy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect