Characterization of Interleukin-15-Transpresenting Dendritic Cells for Clinical Use

J Immunol Res. 2017:2017:1975902. doi: 10.1155/2017/1975902. Epub 2017 Jul 13.

Abstract

Personalized dendritic cell- (DC-) based vaccination has proven to be safe and effective as second-line therapy against various cancer types. In terms of overall survival, there is still room for improvement of DC-based therapies, including the development of more immunostimulatory DC vaccines. In this context, we redesigned our currently clinically used DC vaccine generation protocol to enable transpresentation of interleukin- (IL-) 15 to IL-15Rβγ-expressing cells aiming at boosting the antitumor immune response. In this study, we demonstrate that upon electroporation with both IL-15 and IL-15Rα-encoding messenger RNA, mature DC become highly positive for surface IL-15, without influencing the expression of prototypic mature DC markers and with preservation of their cytokine-producing capacity and their migratory profile. Functionally, we show that IL-15-transpresenting DC are equal if not better inducers of T-cell proliferation and are superior in tumor antigen-specific T-cell activation compared with DC without IL-15 conditioning. In view of the clinical use of DC vaccines, we evidence with a time- and cost-effective manner that clinical grade DC can be safely engineered to transpresent IL-15, hereby gaining the ability to transfer the immune-stimulating IL-15 signal towards antitumor immune effector cells.

MeSH terms

  • Cancer Vaccines / immunology*
  • Cell Differentiation
  • Cell Proliferation
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / physiology
  • Electroporation
  • Humans
  • Immunotherapy, Adoptive
  • Interleukin-15 / administration & dosage
  • Interleukin-15 / genetics*
  • Interleukin-15 / immunology*
  • Interleukin-15 Receptor alpha Subunit / administration & dosage
  • Interleukin-15 Receptor alpha Subunit / genetics
  • Interleukin-15 Receptor alpha Subunit / immunology
  • Lymphocyte Activation
  • Transfection

Substances

  • Cancer Vaccines
  • Cytokines
  • IL15 protein, human
  • Interleukin-15
  • Interleukin-15 Receptor alpha Subunit