Noninvasive dual modality in vivo monitoring of the persistence and potency of a tumor targeted conditionally replicating adenovirus.
In clinical trials with cancer patients, the safety of conditionally replicating adenoviruses (CRAds) has been good. However, marginal data are available on the persistence or antitumor efficacy of these agents. The oncolytic potency of CRAds is determined by their capacity for entering target cells. Consequently, we constructed a retargeted CRAd featuring a secreted marker protein, soluble human carcinoembryogenic antigen (hCEA), which can be measured in growth medium or plasma. We found that virus replication closely correlated with hCEA secretion both in vitro and in vivo. Further, antitumor efficacy and the persistence of the virus could be deduced from plasma hCEA levels. Finally, using in vivo bioluminescence imaging, we were able to detect effective tumor cell killing by the virus, which led to enhanced therapeutic efficacy.
Kanerva
A
A
Cancer Gene Therapy Group, Rational Drug Design, Biomedicum Helsinki, University of Helsinki, Finland.
Zinn
K R
KR
Peng
K-W
KW
Ranki
T
T
Kangasniemi
L
L
Chaudhuri
T R
TR
Desmond
R A
RA
Wang
M
M
Takayama
K
K
Hakkarainen
T
T
Alfthan
H
H
Stenman
U-H
UH
Curiel
D T
DT
Hemminki
A
A
D000230:Adenocarcinoma / Q000097:blood / Q000628:therapy* / Q000821:virology; D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000097:blood / Q000628:therapy* / Q000821:virology; D016896:Treatment Outcome; D014779:Virus Replication
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen