INGN 007, an oncolytic adenovirus vector, replicates in Syrian hamsters but not mice: comparison of biodistribution studies.
Preclinical biodistribution studies with INGN 007, an oncolytic adenovirus (Ad) vector, supporting an early stage clinical trial were conducted in Syrian hamsters, which are permissive for Ad replication, and mice, which are a standard model for assessing toxicity and biodistribution of replication-defective (RD) Ad vectors. Vector dissemination and pharmacokinetics following intravenous administration were examined by real-time PCR in nine tissues and blood at five time points spanning 1 year. Select organs were also examined for the presence of infectious vector/virus. INGN 007 (VRX-007), wild-type Ad5 and AdCMVpA (an RD vector) were compared in the hamster model, whereas only INGN 007 was examined in mice. DNA of all vectors was widely disseminated early after injection, but decayed rapidly in most organs. In the hamster model, DNA of INGN 007 and Ad5 was more abundant than that of the RD vector AdCMVpA at early times after injection, but similar levels were seen later. An increased level of INGN 007 and Ad5 DNA but not AdCMVpA DNA in certain organs early after injection, and the presence of infectious INGN 007 and Ad5 in lung and liver samples at early times after injection, strongly suggests that replication of INGN 007 and Ad5 occurred in several Syrian hamster organs. There was no evidence of INGN 007 replication in mice. In addition to providing important information about INGN 007, the results underscore the utility of the Syrian hamster as a permissive immunocompetent model for Ad5 pathogenesis and oncolytic Ad vectors.
Ying
B
B
VirRx Inc., St Louis, MO 63108, USA.
Toth
K
K
Spencer
J F
JF
Meyer
J
J
Tollefson
A E
AE
Patra
D
D
Dhar
D
D
Shashkova
E V
EV
Kuppuswamy
M
M
Doronin
K
K
Thomas
M A
MA
Zumstein
L A
LA
Wold
W S M
WS
Lichtenstein
D L
DL
D000256:Adenoviridae / Q000502:physiology*; D000818:Animals; D006224:Cricetinae; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008099:Liver / Q000821:virology; D008168:Lung / Q000821:virology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009369:Neoplasms / Q000628:therapy; D050504:Oncolytic Viruses; D013045:Species Specificity; D014779:Virus Replication
D004279:DNA, Viral