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Titolo:
An adenovirus with enhanced infectivity mediates molecular chemotherapy ofovarian cancer cells and allows imaging of gene expression
Autore:
Hemminki, A; Belousova, N; Zinn, KR; Liu, B; Wang, MH; Chaudhuri, TR; Rogers, BE; Buchsbaum, DJ; Siegal, GP; Barnes, MN; Gomez-Navarro, J; Curiel, DT; Alvarez, RD;
Indirizzi:
Univ Alabama, Dept Med, Div Human Gene Therapy, Gene Therapy Ctr, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 herapy Ctr, Birmingham, AL 35294 USA Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ept Pathol, Birmingham, AL 35294 USA Univ Alabama, Dept Surg, Birmingham, AL 35294 USA Univ Alabama BirminghamAL USA 35294 Dept Surg, Birmingham, AL 35294 USA Univ Alabama, Dept Radiol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ept Radiol, Birmingham, AL 35294 USA Univ Alabama, Dept Radiat Oncol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 diat Oncol, Birmingham, AL 35294 USA Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 Cell Biol, Birmingham, AL 35294 USA Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 & Gynecol, Birmingham, AL 35294 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 3, volume: 4, anno: 2001,
pagine: 223 - 231
SICI:
1525-0016(200109)4:3<223:AAWEIM>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSGENE EXPRESSION; IMMUNE-RESPONSES; AIRWAY EPITHELIA; CARCINOMA CELLS; NECK-CANCER; IN-VITRO; THERAPY; RECEPTOR; VECTOR; DELIVERY;
Keywords:
cancer; gene therapy; ovarian cancer; adenovirus; thymidine kinase; somatostatin receptor; imaging; targeting;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Hemminki, A Univ Alabama, Dept Med, Div Human Gene Therapy, Gene Therapy Ctr, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 Birmingham, AL 35294 USA
Citazione:
A. Hemminki et al., "An adenovirus with enhanced infectivity mediates molecular chemotherapy ofovarian cancer cells and allows imaging of gene expression", MOL THER, 4(3), 2001, pp. 223-231

Abstract

The adenovirus (Ad) is a useful vector for cancer gene therapy due to its unparalleled gene transfer efficiency to dividing and quiescent cells. Primary cancer cells, however, often have highly variable or low levels of the requisite coxsackie-adenovirus receptor (CAR). Also, assessment of gene transfer and vector persistence has been logistically difficult in human clinical trials. We describe here two novel bicistronic adenoviral (Ad) vectors,AdTKSSTR and RGDTKSSTR, which contain the herpes simplex virus thymidine kinase gene (TK) for molecular chemotherapy and bystander effect. In addition, the viruses contain the human somatostatin receptor subtype-2 gene (SSTR2), the expression of which can be noninvasively imaged. We enhanced the infectivity of RGDTKSSTR by genetically incorporating the RGD-4C motif into the HI-loop of the fiber. This allows the virus to circumvent CAR deficiencyby binding to alpha (v)beta (3), and alpha (v)beta (5) integrins, which are highly expressed on most ovarian cancers. The expanded tropism of RGDTKSSTR results in increased infectivity of purified primary ovarian cancer cells and allows enhanced gene transfer in the presence of malignant ascites containing anti-Ad antibodies. RGDTKSSTR may be a useful agent for treating ovarian cancer in clinical trials.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/06/20 alle ore 18:54:53