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

• Published in: World journal of gastroenterology : WJG 2013-08, Vol.19 (31), p.5138-5143
• Main Authors: Liu, Hao, Yuan, Shou-Jun, Chen, Ying-Tai, Xie, Yi-Bin, Cui, Liang, Yang, Wei-Zhi, Yang, De-Xuan, Tian, Yan-Tao
• Format: Article
• Language: English
• Subjects: Animals; Brief; Cell Line, Tumor; Female; Genetic Therapy; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Mice; Mice, Inbred C57BL; Oncolytic Virotherapy; Pancreatic Neoplasms; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Pancreatic Neoplasms - virology; Simplexvirus - genetics; Simplexvirus - metabolism; Time Factors; Tumor Burden
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v19.i31.5138

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. 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). 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. 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.