Preclinical evaluation of herpes simplex virus armed with granulocyte-macrophage colony-stimulating factor in pancreatic carcinoma.

Abstract

AIM:

To investigate the therapeutic efficacy and mechanisms of action of oncolytic-herpes-simplex-virus encoding granulocyte-macrophage colony-stimulating factor (HSV(GM-CSF)) in pancreatic carcinoma.

METHODS:

Tumor blocks were homogenized in a sterile grinder in saline. The homogenate was injected into the right armpit of each mouse. After vaccination, the mice were randomly assigned into four groups: a control group, a high dose HSV(GM-CSF) group [1 × 10⁷ plaque forming units (pfu)/tumor], a medium dose HSV(GM-CSF) group (5 × 10⁶ pfu/tumor) and a low dose HSV(GM-CSF) group (5 × 10⁵ pfu/tumor). After initiation of drug administration, body weights and tumor diameters were measured every 3 d. Fifteen days later, after decapitation of the animal by cervical dislocation, each tumor was isolated, weighed and stored in 10% formaldehyde solution. The drug effectiveness was evaluated according to the weight, volume and relative volume change of each tumor. Furthermore, GM-CSF protein levels in serum were assayed by enzyme-linked immunosorbent assays at 1, 2, 3 and 4 d after injection of HSV(GM-CSF).

RESULTS:

Injection of the recombinant mouse HSV encoding GM-CSF resulted in a significant reduction in tumor growth compared to the control group, and dose-dependent effects were observed: the relative tumor proliferation rates of the low dose, medium dose and high dose groups on 15 d after injection were 45.5%, 55.2% and 65.5%, respectively. The inhibition rates of the tumor weights of the low, middle, and high dose groups were 41.4%, 46.7% and 50.5%, respectively. Furthermore, the production of GM-CSF was significantly increased in the mice infected with HSV(GM-CSF). The increase in the GM-CSF level was more pronounced in the high dose group compared to the other two dose groups.

CONCLUSION:

Our study provides the first evidence that HSV(GM-CSF) could inhibit the growth of pancreatic cancer. The enhanced GM-CSF expression might be responsible for the phenomenon.

• Authors: Hao Liu, Shou-Jun Yuan, Ying-Tai Chen, Yi-Bin Xie, Liang Cui, Wei-Zhi Yang, De-Xuan Yang, Yan-Tao Tian
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 19 Issue 31 Pg. 5138-43 (Aug 21 2013) ISSN: 2219-2840 [Electronic] United States
• PMID: 23964149 (Publication Type: Journal Article)

Chemical References

• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• Cell Line, Tumor
• Female
• Genetic Therapy
• Granulocyte-Macrophage Colony-Stimulating Factor (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Oncolytic Virotherapy
• Pancreatic Neoplasms (genetics, metabolism, pathology, therapy, virology)
• Simplexvirus (genetics, metabolism)
• Time Factors
• Tumor Burden