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

Farzan Siddiqui, E. J. Ehrhart, Brad Charles, Laura Chubb, Chuan Yuan Li, Xiuwu Zhang, Susan M. Larue, Paul R. Avery, Mark W. Dewhirst, Robert L. Ullrich

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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-γ (IFN-γ) 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-γ, IP-10, VEGF and PAI-1) was also studied.

Original languageEnglish (US)
Pages (from-to)587-606
Number of pages20
JournalInternational Journal of Hyperthermia
Volume22
Issue number7
DOIs
StatePublished - Nov 2006
Externally publishedYes

Fingerprint

Induced Hyperthermia
Interleukin-12
Chemokine CXCL10
Genes
Neoplasms
Plasminogen Activator Inhibitor 1
Cytokines
Vascular Endothelial Growth Factor A
Shock
Immunization
Hot Temperature
Angiogenesis Inducing Agents
Baths
Heating
Interferons
Control Groups
Water

Keywords

  • Anti-angiogenesis
  • Hyperthermia
  • Interleukin-12

ASJC Scopus subject areas

  • Cancer Research
  • Radiological and Ultrasound Technology

Cite this

Siddiqui, F., Ehrhart, E. J., Charles, B., Chubb, L., Li, C. Y., Zhang, X., ... Ullrich, R. L. (2006). Anti-angiogenic effects of interleukin-12 delivered by a novel hyperthermia induced gene construct. International Journal of Hyperthermia, 22(7), 587-606. https://doi.org/10.1080/02656730600983063

Anti-angiogenic effects of interleukin-12 delivered by a novel hyperthermia induced gene construct. / Siddiqui, Farzan; Ehrhart, E. J.; Charles, Brad; Chubb, Laura; Li, Chuan Yuan; Zhang, Xiuwu; Larue, Susan M.; Avery, Paul R.; Dewhirst, Mark W.; Ullrich, Robert L.

In: International Journal of Hyperthermia, Vol. 22, No. 7, 11.2006, p. 587-606.

Research output: Contribution to journalArticle

Siddiqui, F, Ehrhart, EJ, Charles, B, Chubb, L, Li, CY, Zhang, X, Larue, SM, Avery, PR, Dewhirst, MW & Ullrich, RL 2006, 'Anti-angiogenic effects of interleukin-12 delivered by a novel hyperthermia induced gene construct', International Journal of Hyperthermia, vol. 22, no. 7, pp. 587-606. https://doi.org/10.1080/02656730600983063
Siddiqui, Farzan ; Ehrhart, E. J. ; Charles, Brad ; Chubb, Laura ; Li, Chuan Yuan ; Zhang, Xiuwu ; Larue, Susan M. ; Avery, Paul R. ; Dewhirst, Mark W. ; Ullrich, Robert L. / Anti-angiogenic effects of interleukin-12 delivered by a novel hyperthermia induced gene construct. In: International Journal of Hyperthermia. 2006 ; Vol. 22, No. 7. pp. 587-606.
@article{bde06463f29b44788bd19de736485ea2,
title = "Anti-angiogenic effects of interleukin-12 delivered by a novel hyperthermia induced gene construct",
abstract = "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-γ (IFN-γ) 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-γ, IP-10, VEGF and PAI-1) was also studied.",
keywords = "Anti-angiogenesis, Hyperthermia, Interleukin-12",
author = "Farzan Siddiqui and Ehrhart, {E. J.} and Brad Charles and Laura Chubb and Li, {Chuan Yuan} and Xiuwu Zhang and Larue, {Susan M.} and Avery, {Paul R.} and Dewhirst, {Mark W.} and Ullrich, {Robert L.}",
year = "2006",
month = "11",
doi = "10.1080/02656730600983063",
language = "English (US)",
volume = "22",
pages = "587--606",
journal = "International Journal of Hyperthermia",
issn = "0265-6736",
publisher = "Informa Healthcare",
number = "7",

}

TY - JOUR

T1 - Anti-angiogenic effects of interleukin-12 delivered by a novel hyperthermia induced gene construct

AU - Siddiqui, Farzan

AU - Ehrhart, E. J.

AU - Charles, Brad

AU - Chubb, Laura

AU - Li, Chuan Yuan

AU - Zhang, Xiuwu

AU - Larue, Susan M.

AU - Avery, Paul R.

AU - Dewhirst, Mark W.

AU - Ullrich, Robert L.

PY - 2006/11

Y1 - 2006/11

N2 - 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-γ (IFN-γ) 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-γ, IP-10, VEGF and PAI-1) was also studied.

AB - 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-γ (IFN-γ) 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-γ, IP-10, VEGF and PAI-1) was also studied.

KW - Anti-angiogenesis

KW - Hyperthermia

KW - Interleukin-12

UR - http://www.scopus.com/inward/record.url?scp=33750572453&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750572453&partnerID=8YFLogxK

U2 - 10.1080/02656730600983063

DO - 10.1080/02656730600983063

M3 - Article

VL - 22

SP - 587

EP - 606

JO - International Journal of Hyperthermia

JF - International Journal of Hyperthermia

SN - 0265-6736

IS - 7

ER -