Human adenovirus replicates in immunocompetent models of pancreatic cancer in Syrian hamsters.
The preclinical evaluation of toxicity and antitumor effect of conditionally replicative (oncolytic) adenoviruses is hampered by the inability of human adenoviruses to replicate efficiently in murine cells. The Syrian golden hamster (Mesocricetus auratus) has been suggested as a permissive animal for adenoviral replication, and cancer cell lines derived from various hamster tumors are available. We provide evidence that wild-type adenovirus type 5 is able to infect and replicate in the pancreatic cancer cell lines HaP-T1 and H2T both in vitro and in vivo. Determination of cytopathic effect, viral spread, progeny production, and the expression of late viral proteins indicates that the complete viral cycle of adenovirus takes place, albeit less efficiently than in highly permissive human cancer cell lines A549 and HuH7. Intrahepatic inoculation of HaP-T1 and H2T cells gave rise to tumors in the liver of hamsters that resemble metastases of pancreatic cancer. The growth of HaP-T1-induced nodules was faster compared with those derived from H2T, but both caused progressive liver infiltration and peritoneal dissemination. When adenovirus was inoculated in these lesions, productive replication took place and newly formed infective virions could be recovered 4 days after administration. In conclusion, the Syrian hamster models described here offer the opportunity to evaluate the effect of oncolytic adenoviruses in an immunocompetent animal and may be a valuable tool in the preclinical evaluation of these agents.
Gene Therapy Unit, Center for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain.
Sergia
S
Bortolanza
Pilar
P
Alzuguren
Maria
M
Buñuales
Cheng
C
Qian
Jesus
J
Prieto
Ruben
R
Hernandez-Alcoceba
D000256:Adenoviridae / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D006801:Humans; D008647:Mesocricetus; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000276:immunology / Q000821:virology; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000821:virology*; D014779:Virus Replication / Q000502:physiology*