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.
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.
Authors: Tsutomu Sugahara; J van der Zee; Harm H Kampinga; Zeliko Vujaskovic; Motoharu Kondo; Takeo Ohnishi; Gloria Li; Heon J Park; Dennis B Leeper; Valentina Ostapenko; Elizabeth A Repasky; Masami Watanabe; Chang W Song Journal: Int J Hyperthermia Date: 2008-03 Impact factor: 3.914
Authors: Alexander Moncion; Jonah S Harmon; Yan Li; Sam Natla; Easton C Farrell; Oliver D Kripfgans; Jan P Stegemann; Francisco M Martín-Saavedra; Nuria Vilaboa; Renny T Franceschi; Mario L Fabiilli Journal: Biomaterials Date: 2018-12-13 Impact factor: 12.479
Authors: E Antonio Chiocca; John S Yu; Rimas V Lukas; Isaac H Solomon; Keith L Ligon; Hiroshi Nakashima; Daniel A Triggs; David A Reardon; Patrick Wen; Brittany M Stopa; Ajay Naik; Jeremy Rudnick; Jethro L Hu; Priya Kumthekar; Bakhtiar Yamini; Jill Y Buck; Nathan Demars; John A Barrett; Arnold B Gelb; John Zhou; Francois Lebel; Laurence J N Cooper Journal: Sci Transl Med Date: 2019-08-14 Impact factor: 17.956
Authors: Farzan Siddiqui; Andrew Kolozsvary; Kenneth N Barton; Svend O Freytag; Stephen L Brown; Jae Ho Kim Journal: Int J Hyperthermia Date: 2009-06 Impact factor: 3.914