Biodegradable polymer-based interleukin-12 gene delivery: Role of induced cytokines, tumor infiltrating cells and nitric oxide in anti-tumor activity

A. Maheshwari, S. Han, R. I. Mahato, S. W. Kim

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

The objective of this study was to investigate the role of induced cytokines, tumor infiltrating cells and nitric oxide (NO) in anti-tumor activity upon intratumoral injection of free and condensed plasmid DNA encoding murine interleukin-12 (pmIL-12) into BALB/c mice bearing subcutaneous tumors. Poly[α-(4-aminobutyl)-L-glycolic acid] (PAGA) was used for complex formation with pmIL-12 in presence of 5% (w/v) glucose. Upon characterization, PAGA/pmIL-12 (3/1, ±) complexes were found to be most effective in gene transfer and were used consistently throughout this study. The levels of mIL-12 p70 and induced cytokines were determined by ELISA in the supernatant of the cultured tumors of the CT-26 subcutaneous tumor bearing BALB/c female mice 48 h after intratumoral injection of PAGA/pmIL-12 complexes and naked pmIL-12. The levels of IL-12, IFN-γ, TNF-α and NO were higher for the PAGA/pmIL-12 complexes than those for the naked pmIL-12, PAGA alone and 5% glucose injected groups. The relative presence of natural killer (NK) cells, CD4+ T cells, and antigen presenting cells, such as macrophages and dendritic cells determined using immunohistochemistry was higher for PAGA/pmIL-12 complexes compared with naked pmIL-12. The presence of CMV promoter in plasmid encoding IL-12 cDNAs did not induce any type I interferon response. There was a significant improvement in the survival rate and the inhibition of tumor growth after repeated injections of PAGA/pmIL-12 complexes.

Original languageEnglish (US)
Pages (from-to)1075-1084
Number of pages10
JournalGene Therapy
Volume9
Issue number16
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Biodegradable cationic polymer
  • Gene expression
  • Interleukin-12
  • Tumor regression
  • Tumor-infiltrating cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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