A Cytokine Cocktail Augments the Efficacy of Adoptive NK-92 Cell Therapy Against Mouse Xenografts of Human Cancer

Anticancer Res. 2016 Jul;36(7):3373-82.

Abstract

Background/aim: Peripheral blood mononuclear cells (PBMCs) activated with immobilized monoclonal antibody against cluster of differentiation 3 (CD3) secrete cytokines in their culture supernatant (termed ACD3S). We examined the antitumor efficacy of ACD3S-activated NK-92 cells in vitro and in vivo.

Materials and methods: Interleukin (IL) 2-depleted NK-92 cells were reactivated with ACD3S, analyzed for their phenotype and tested for cytotoxicity, and perforin and interferon γ (IFNγ) production. Severe combined immunodeficient (SCID) mice xenografted with human melanoma and breast cancer cells were treated with ACD3S-activated NK-92 cells and tumor growth was monitored.

Results: Brief activation of IL2-depleted NK-92 cells with ACD3S fully restored their in vitro cytotoxicity towards tumor cells. ACD3S-activated NK-92 cells were phenotypically similar to standard NK-92 cells, but exhibited prolonged cytotoxicity and produced higher levels of IFNγ. When adoptively transferred to tumor-bearing SCID mice, these cells retarded the growth of melanoma and breast tumors.

Conclusion: Stimulation of NK-92 cells with ACD3S may be useful in clinical cancer therapy, as an alternative method for ex vivo natural killer cell activation.

Keywords: Conditioned medium; NK-92; SCID mice; cytotoxicity.

MeSH terms

  • Animals
  • Antibodies, Immobilized / immunology
  • Antibodies, Monoclonal / immunology
  • Breast Neoplasms / immunology
  • Breast Neoplasms / therapy*
  • CD3 Complex / immunology
  • Cytokines / administration & dosage
  • Cytokines / immunology*
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / transplantation*
  • Leukocytes, Mononuclear / immunology
  • Lymphoma, Non-Hodgkin / pathology
  • MCF-7 Cells
  • Melanoma / immunology
  • Melanoma / therapy*
  • Mice
  • Mice, SCID
  • Random Allocation
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Immobilized
  • Antibodies, Monoclonal
  • CD3 Complex
  • Cytokines