Evaluation of adenovirus vectors containing serotype 35 fibers for tumor targeting.
Cancer Gene Ther
; 13(12): 1072-81, 2006 Dec.
Article
em En
| MEDLINE
| ID: mdl-16874361
ABSTRACT
There is growing evidence from in vitro studies that subgroup B adenoviruses (Ad) can overcome the limitations in safety and tumor transduction efficiency seen with commonly used subgroup C serotype 5-based vectors. In this study, we confirm that the expression level of the B-group Ad receptor, CD46, correlates with the grade of malignancy of cervical cancer in situ. We also demonstrate the in vivo properties of Ad5-based vectors that contain the B-group Ad serotype 35 fiber (Ad5/35) in transgenic mice that express CD46 in a pattern and at a level similar to humans. Upon intravenous and intraperitoneal injection, an Ad5/35 vector did not efficiently transduce normal tissue, but was able to target metastatic or intraperitoneal tumors that express CD46 at levels comparable to human tumors. When an oncolytic Ad5/35-based vector was employed, in both tumor models antitumor effects were observed. Furthermore, injection of Ad5/35 vectors into CD46 transgenic mice caused less innate toxicity than Ad5 vectors. Our data demonstrate that Ad vectors that target CD46 offer advantages over Ad5-based vectors for treatment of cancer.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Adenoviridae
/
Vetores Genéticos
/
Neoplasias
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cancer Gene Ther
Assunto da revista:
GENETICA MEDICA
/
NEOPLASIAS
/
TERAPEUTICA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos