Establishment of Novel Cells Stably Secreting Various Human IL-18 Recombinant Proteins

Curr Pharm Biotechnol. 2019;20(1):47-55. doi: 10.2174/1389201020666190206203640.

Abstract

Background: The immunotherapies against cancer, autoinmmune diseases or infection are remarkable development. These days programmed cell death (PD)-1 antibody-induced immune checkpoint blockade or chimeric antigen receptor-T cells (CAR-T) have been shown to have eminent therapeutic effects on tumor development. We have focused on adoptive transfer with human gamma delta T cells for novel immunotherapies. Additionally, IL-18 is one of the cytokines that enhances cytokine secretion and cytotoxicity of human gamma delta T cells.

Method: Thus, we established novel cell lines stably expressing and secreting various types of human recombinant IL-18 proteins to their culture supernatants using episomal vector. We also differentiated primary cultured human gamma delta T cells from peripheral blood mononuclear leukocytes to validate biological activity of the IL-18 proteins using measuring IFN-γ by ELISA.

Results and conclusion: Finally, we demonstrated that the supernatant could activate human gamma delta T cells using monitoring interferon gamma in culture medium.

Keywords: EBNA1; IFN-γ; IL-18; OriP; conditioned medium; human gamma delta T cells..

MeSH terms

  • Amino Acid Sequence
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism
  • HEK293 Cells
  • Humans
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology
  • Interleukin-18 / metabolism*
  • Intraepithelial Lymphocytes / immunology
  • Intraepithelial Lymphocytes / metabolism*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism*
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / immunology
  • Receptors, Chimeric Antigen / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Cytokines
  • IL18 protein, human
  • Interleukin-18
  • Receptors, Chimeric Antigen
  • Recombinant Proteins