The effects of interleukin 2 and rAd-p53 as a treatment for glioblastoma

Mol Med Rep. 2018 Mar;17(3):4853-4859. doi: 10.3892/mmr.2018.8408. Epub 2018 Jan 9.

Abstract

Interleukin 2 (IL-2) is an anti-cancer cytokine that stimulates T cell propagation, triggering innate and adaptive immunity. IL-2 has been used for cancer therapy and has achieved curative effects. Recombinant adenovirus p53 injection (rAd‑p53) is a gene therapeutic agent that may improve the prognosis of patients with glioblastoma (GBM). In the present study, the effect of combined IL‑2 and rAd‑p53 treatment was studied. The ability of IL‑2 to stimulate immunoregulation and the ability of p53 to induce apoptosis for GBM was researched in the GBM tumor model. In addition, the activity of IL‑2 was analyzed. The antitumor potential of IL‑2 and rAd‑p53 was studied using xenograph mice carrying GBM cells. Tumor‑specific CD4+ and CD8+ T cells were also analyzed in the GBM‑bearing models. The results demonstrated that IL‑2 and rAd‑p53 not only stimulated tumor‑specific cytotoxic T‑lymphocyte responses and increased regulatory CD4+ and cytotoxic CD8+ T cell proliferation, however additionally increased expression of apoptosis‑associated genes. The treatment with IL‑2 and rAd‑p53 resulted in tumor regression and prolonged the survival of glioma‑bearing mice. Taken together, a combination of IL‑2 and rAd‑p53 treatment combines the effects of immunotherapy and oncolytic therapy and may be a comprehensive therapeutic schedule for clinical application in future cancer therapies.

Keywords: interleukin 2; rAd-p53; glioblastoma; immunoregulation; apoptosis; combined treatment.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 8 / genetics
  • Caspase 8 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Disease Models, Animal
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Humans
  • Interleukin-2 / pharmacology
  • Interleukin-2 / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Interleukin-2
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Caspase 3
  • Caspase 8
  • Caspase 9