Interleukin-24 enhancing antitumor activity of chimeric oncolytic adenovirus for treating acute promyelocytic leukemia cell

Medicine (Baltimore). 2019 May;98(22):e15875. doi: 10.1097/MD.0000000000015875.

Abstract

Background: Acute promyelocytic leukaemia (APL) is a clonal disease arising by hematopoietic stem cell (HSC), which characterized by inappropriate proliferation/differentiation or survival of immature myeloid progenitors. Oncolytic adenoviruses have been under widespread investigation as anticancer agents. Recently, our data suggested that tumor cells were cured by AdCN205-IL-24, an adenovirus serotype 5-based conditionally replicating adenovirus expressing IL-24 after infection.

Methods: In this study, we created a novel fiber chimeric oncolytic adenovirus AdCN306-IL-24 that has Ad11 tropism and approved CAR (coxsackie adenovirus receptor, CAR)-independent cell entry, which could allow development of selective cytopathic effects (CPE) in APL cells in vitro.

Results: Formidable cytotoxic effect was specifically implemented in APL cells after infection with AdCN306-IL-24. The expression of IL-24 was up-regulated upon treated with accepted tumors. And the vector also induced superior cytolytic effects activity in APL cells by activation of programmed cell death.

Conclusions: Taken together, our data suggested that chimeric oncolytic adenovirus AdCN306-IL-24 could express IL-24 gene, representing a potential therapeutics for acute promyelocytic leukemia.

MeSH terms

  • Adenovirus Early Proteins / genetics
  • Adenovirus Early Proteins / pharmacology*
  • Chimera
  • HEK293 Cells
  • HL-60 Cells
  • Humans
  • Interleukins / metabolism*
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / immunology
  • Oncolytic Virotherapy / methods*
  • Oncolytic Viruses / immunology*

Substances

  • Adenovirus Early Proteins
  • Interleukins
  • interleukin-24