Assessment of a capsid-modified E1B 55-kDa protein-deficient adenovirus vector for tumor treatment
- VernacularTitle:嵌合型E1B 55-kDa蛋白缺陷型腺病毒载体治疗肿瘤的评价
- Author:
Xun YE
;
Qin LU
;
Yi ZHAO
;
Zhen REN
;
Xia MENG
;
Shengfang GE
;
Qihong QIU
;
Yong TONG
;
Andre LIEBER
;
Min LIANG
;
Fang HU
;
Hongzhuan CHEN
- Publication Type:Journal Article
- Keywords:
adenovirus;
transductional control;
oncolytic
- From:
Progress in Biochemistry and Biophysics
2005;32(12):1156-1164
- CountryChina
- Language:Chinese
-
Abstract:
ONYX-015 and H101 are E1B 55-kDa protein-deficient replicating C group adenoviruses that are currently in clinical trials as antitumor agents. However, their application in cancer gene therapy is limited by the native tropism of C group adenoviruses. This is in part due to low expression of the C group adenovirus receptor (coxsackievirus-adenovirus receptor, CAR) on malignant tumors. An H101-based chimeric virus vector containing sequences encoding the Ad35 fiber domain instead of the Ad5 fiber (H101-F35) was constructed. This modification allowed infection of tumor cells through CD46, a membrane protein over-expressed on tumors. The CAR and CD46 RNA expression was evaluated by RT-PCR method. H101-F35 conferred a stronger cytocidal effect than H101 and ONYX-015 in tumor cell lines that lacked CAR expression (MDA-MB-435 and MCF-7), while the cytocidal effect of H101-35, H101 and ONYX-015 was similar in high-level CAR expressing cancer cell lines (A549, NCI-H446, Hep3B, LNCaP, ZR-75-30 and Bcap-37). In an MDA-MB-435 xenograft mouse tumor model, tumor growth in mice receiving H101-F35 was significantly inhibited compared with mice injected with H101. These results suggest that the chimeric oncolytic adenovirus H101-F35 vector might be a useful candidate for gene therapy of cancer.
