Ligand-Mediated Targeting of Cytokine Interleukin-27 Enhances Its Bioactivity In Vivo

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Marxa L Figueiredo1,2, Manoel Figueiredo Neto1, Janelle Wes Salameh1,2

  • 1Department of Basic Medical Sciences, Purdue University, 625 Harrison Street, LYNN 2177, West Lafayette, IN 47907, USA.

Molecular Therapy. Methods & Clinical Development
|April 30, 2020
PubMed

Insights

Targeted interleukin-27 (IL-27) gene delivery effectively reduced prostate tumor growth in mice. This novel approach enhanced immune cell infiltration and cytokine bioactivity, showing improved therapeutic potential.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Interleukin-27 (IL-27) is a cytokine with demonstrated potential in halting tumor growth and mediating regression across various cancer models.
  • Prostate cancer remains a significant health concern, necessitating novel therapeutic strategies.
  • Targeting cytokines can enhance their bioactivity and therapeutic efficacy.

Purpose of the Study:

  • To investigate the efficacy of a novel targeted interleukin-27 (IL-27) gene delivery system for prostate cancer treatment.
  • To evaluate the impact of a dual-targeting heptapeptide modification on IL-27 bioactivity.
  • To assess the antitumor effects of targeted IL-27 via sonodelivery in a preclinical prostate cancer model.

Main Methods:

  • Utilized sonoporation (sonodelivery) for targeted IL-27 gene delivery in an immunocompetent TC2R C57/BL6 mouse model.
  • Assessed IL-27 bioactivity using STAT1 and Interferon-gamma (IFN-γ) reporter genes.
  • Quantified tumor growth, effector cellular profiles (NKT and CD8 cells), and antitumor effects.

Main Results:

  • Targeted IL-27 gene delivery significantly reduced prostate tumor growth compared to untargeted IL-27.
  • Enhanced bioactivity of targeted IL-27 was confirmed through reporter gene expression.
  • Increased accumulation of Natural Killer T (NKT) and CD8 effector cells was observed within tumors.

Conclusions:

  • A novel IL-27-based targeting strategy demonstrates improved therapeutic efficacy in prostate cancer.
  • Sonodelivery provides a simple and effective method for targeted cytokine gene delivery.
  • Targeted IL-27 holds promise as a potent immunotherapy for prostate cancer.
Keywords:
IL-6Rαheptapeptideinterleukin-27ligand-mediated targetingprostate cancersonoporation delivery

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