Cotton rat tumor model for the evaluation of oncolytic adenoviruses.
Oncolytic human adenovirus (Ad) vectors exert their antitumor effect by replicating in and lysing tumor cells. These vectors are commonly evaluated in immunodeficient mice bearing human tumor xenografts. However, this model suffers because the mice are immunodeficient and are not permissive for human Ads. We have developed a cotton rat model to test the selectivity, immunogenicity, and efficacy of oncolytic Ad vectors. The cotton rat is a rodent species that is semipermissive for human Ads. We show that the cotton cancer rat cell line LCRT supports the replication of human Ad in tissue culture and that the cells are destroyed on virus replication. When injected subcutaneously, LCRT cells formed tumors in immunocompetent cotton rats, and the growth of these tumors was delayed by the injection of an oncolytic Ad vector. Replication of the Ad vector in the tumor was demonstrated by sampling tumor tissue and isolating infectious virus particles at various times after intratumoral injection of the virus. We propose that the cotton rat can be used as an animal model to evaluate oncolytic Ad vectors.
Toth
Karoly
K
Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine, St. Louis, MO 63104, USA.
Spencer
Jacqueline F
JF
Tollefson
Ann E
AE
Kuppuswamy
Mohan
M
Doronin
Konstantin
K
Lichtenstein
Drew L
DL
La Regina
Marie C
MC
Prince
Gregory A
GA
Wold
William S M
WS
D000258:Adenovirus Infections, Human / Q000628:therapy / Q000821:virology; D000260:Adenoviruses, Human / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000628:therapy* / Q000821:virology; D051381:Rats; D016205:Sigmodontinae; D014779:Virus Replication / Q000502:physiology