[Effect of expression of coxsackie and adenovirus receptor on antitumor activity of genetically modified adenovirus].
OBJECTIVE
The effect of adenovirus, a kind of oncolytic virus and a kind of carrier in gene therapy, depends on the expression of Coxsackie and adenovirus receptor (CAR) on cell surface to a large degree. This study was to evaluate relationship of CAR expression to infectivity and efficacy of adenovirus.


METHODS
Pathologic specimens from 29 patients in a clinical trial of genetically modified adenovirus (H101) were collected. Expression of CAR in cancer tissues was detected by immuohistochemistry. Expression of CAR on cancer cell membrane was detected by flow cytometry (FCM). Inhibitory effect of H101 on cells was assessed by MTT assay.


RESULTS
Positive rate of CAR was significantly higher in patients achieved complete remission (CR) or partial remission (PR) than in patients had stable disease (SD) or progressive disease (PD) [70.0% (7/10) vs. 31.6% (6/19), P=0.048]. CAR expression on different cells was different, and the amount of CAR was positively related to virus infectivity, presented as the inhibitory rate of H101-infected cells (r=0.986).


CONCLUSIONS
The expression of CAR closely relates to antitumor activity and efficacy of adenovirus. Also, the efficacy of adenovirus is higher on cancers with increased CAR expression than on those with decreased CAR expression.
Yuan
Zhong-Yu
ZY
Department of Medical Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060,P. R. China.
Guan
Zhong-Zhen
ZZ
Zhang
Li
L
Xu
Rui-Hua
RH
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor / Q000378:metabolism / Q000821:virology; D049109:Cell Proliferation; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000628:therapy / Q000821:virology; D005260:Female; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000628:therapy / Q000821:virology; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000628:therapy / Q000821:virology; D011991:Receptors, Virus / Q000378:metabolism*; D012074:Remission Induction
C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus