Syrian hamster as a permissive immunocompetent animal model for the study of oncolytic adenovirus vectors.
Oncolytic adenoviruses represent an innovative approach to cancer therapy. These vectors are typically evaluated in immunodeficient mice with human xenograft tumors. However, in addition to being immunodeficient, this model is limited because normal and cancerous mouse tissues are poorly permissive for human adenovirus replication. This prompted us to search for a model that more accurately reflects the use of oncolytic adenoviruses in cancer patients. To this end, we developed a novel Syrian hamster model that is both immunocompetent and replication-permissive. We found that human adenovirus replicates well in Syrian hamster cell lines and confirmed replication in the lungs. Oncolytic adenovirus injection showed efficacy in three different hamster tumor models. Furthermore, i.t. oncolytic adenovirus injection resulted in suppression of primary and metastatic lesions, i.t. replication and necrosis, vector entrance into the bloodstream, replication in the liver and lungs, and anti-adenovirus antibody induction. Our findings show that the Syrian hamster is a promising immunocompetent model that is permissive to human adenovirus replication in tumors as well as normal tissues. Therefore, the Syrian hamster model may become a valuable tool for the field of oncolytic adenovirus vectors in which vector safety and efficacy can be evaluated.
Thomas
Maria A
MA
Molecular Microbiology and Immunology, Saint Louis University School of Medicine and Division of Comparative Medicine, Washington University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, USA.
Spencer
Jacqueline F
JF
La Regina
Marie C
MC
Dhar
Debanjan
D
Tollefson
Ann E
AE
Toth
Karoly
K
Wold
William S M
WS
D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D006224:Cricetinae; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000235:genetics / Q000493:pharmacokinetics; D006801:Humans; D007121:Immunocompetence; D008168:Lung / Q000821:virology; D008647:Mesocricetus; D014018:Tissue Distribution; D014779:Virus Replication