Anti-angiogenic effects of interleukin-12 delivered by a novel hyperthermia induced gene construct.

Published

Journal Article

PURPOSE: Interleukin-12 (IL-12) is a pro-inflammatory cytokine possessing anti-cancer and anti-angiogenic properties. This study quantitatively assessed the anti-angiogenic effect of IL-12 delivered using an adenoviral vector with murine IL-12 placed under control of a heat shock promoter. This approach limits systemic toxicity by restricting IL-12 delivery locally to the tumour. The kinetics of the downstream cytokines interferon-gamma (IFN-gamma) and interferon inducible protein-10 (IP-10) and other molecules affecting angiogenesis, vascular endothelial growth factor (VEGF) and plasminogen activator inhibitor-1 (PAI-1) were also studied. MATERIALS AND METHODS: 4T1 tumours were grown in Balb/C mice and the AdhspmIL-12 construct was injected intra-tumourally. The tumours were heated after 24 h using a water bath. At various time points post-heating the tumours were collected and quantitatively assessed for cytokine production and vascularity. RESULTS: A significant reduction was seen in the tumour vasculature of the treated group vs. the control group mice. Systemic effects of IL-12 were limited to generalized immunostimulation. No hepatoxicity was noted. CONCLUSIONS: This study suggests that IL-12 can be effectively delivered using a gene-based approach with a heat shock promoter. This results in quantitatively measurable anti-angiogenesis and general immunostimulation. The complex inter-play of other pro- and anti-angiogenic factors (IFN-gamma, IP-10, VEGF and PAI-1) was also studied.

Full Text

Duke Authors

Cited Authors

  • Siddiqui, F; Ehrhart, EJ; Charles, B; Chubb, L; Li, C-Y; Zhang, X; Larue, SM; Avery, PR; Dewhirst, MW; Ullrich, RL

Published Date

  • November 2006

Published In

Volume / Issue

  • 22 / 7

Start / End Page

  • 587 - 606

PubMed ID

  • 17079216

Pubmed Central ID

  • 17079216

International Standard Serial Number (ISSN)

  • 0265-6736

Digital Object Identifier (DOI)

  • 10.1080/02656730600983063

Language

  • eng

Conference Location

  • England