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Titolo:
Selectivity of TAG-72-targeted adenovirus gene transfer to primary ovariancarcinoma cells versus autologous mesothelial cells in vitro
Autore:
Kelly, FJ; Miller, CR; Buchsbaum, DJ; Gomez-Navarro, J; Barnes, MN; Alvarez, RD; Curiel, DT;
Indirizzi:
Univ Alabama, Gene Therapy Ctr, Wallace Tumor Instwaltum, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 Instwaltum, Birmingham, AL 35294 USA Univ Alabama, Dept Med, Div Human Gene Therapy, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ne Therapy, Birmingham, AL 35294 USA Univ Alabama, Dept Pathol, Div Human Gene Therapy, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ne Therapy, Birmingham, AL 35294 USA Univ Alabama, Dept Surg, Div Human Gene Therapy, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ne Therapy, Birmingham, AL 35294 USA Univ Alabama, Dept Obstet Gynecol, Div Gynecol Oncol, Birmingham, AL 35294USA Univ Alabama Birmingham AL USA 35294 necol Oncol, Birmingham, AL 35294USA Univ Alabama, Dept Radiat Oncol, Div Radiat Biol, Birmingham, AL 35294 USAUniv Alabama Birmingham AL USA 35294 adiat Biol, Birmingham, AL 35294 USA Univ Alabama, Dept Surg, Div Neurosurg, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 Neurosurg, Birmingham, AL 35294 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 11, volume: 6, anno: 2000,
pagine: 4323 - 4333
SICI:
1078-0432(200011)6:11<4323:SOTAGT>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
2ND-GENERATION MONOCLONAL-ANTIBODIES; GROWTH-FACTOR RECEPTOR; COXSACKIE-B VIRUSES; CANCER CELLS; INTRAPERITONEAL RADIOIMMUNOTHERAPY; I-131 B72.3; DELIVERY; THERAPY; ANTIGEN; VECTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Kelly, FJ Univ Alabama, Gene Therapy Ctr, Wallace Tumor Instwaltum, Room 620,1824 6th Ave S, Birmingham, AL 35294 USA Univ Alabama Room 620,1824 6th Ave S Birmingham AL USA 35294 USA
Citazione:
F.J. Kelly et al., "Selectivity of TAG-72-targeted adenovirus gene transfer to primary ovariancarcinoma cells versus autologous mesothelial cells in vitro", CLIN CANC R, 6(11), 2000, pp. 4323-4333

Abstract

Efficient gene transfer by recombinant adenovirus (Ad) vectors depends on expression of CAR and or, integrin on target cells. Because Ad may also infect nearby nontarget cells expressing these receptors, such as peritoneal mesothelial cells after i.p. injection, we hypothesized that targeting Ad gene delivery to a receptor overexpressed on most ovarian carcinoma cells, such as TAG-72, would enhance the selectivity of Ad gene transfer when used in this context. A monoclonal antibody that has been investigated clinicallyfor immunotherapy and immunodetection of ovarian carcinomas, namely CC49, was used to construct a bispecific conjugate with the Fab fragment of a neutralizing anti-knob mAb to target Ad binding via TAG-72, This conjugate facilitated TAG-72-specific, CAR-independent Ad reporter gene transfer to bothovarian cancer cell lines and primary ovarian cancer tells cultured from malignant ascites fluid. Fab-CC49 was very selective for tumor cells, augmenting Ad gene transfer to primary ovarian cancer cells 2- to 28-fold relative to untargeted Ad, while also decreasing gene transfer to autologous cultured mesothelial cells 4- to 9-fold. These data suggest that targeting Ad via TAG-72 may improve the selectivity of Ad gene transfer for ovarian tumors8- to 252-fold on i.p. vector injection. These results also define the requirements for a candidate target receptor in the rational design of a targeted Ad vector for ultimate clinical utility, one that selectively infects tumor cells and spares normal cells on i.p. injection. Such a vector may increase gene transfer and decrease the toxicity of Ad vectors, which would improve the therapeutic index of cytotoxic gene therapy for ovarian cancer inclinical trials.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/05/20 alle ore 14:29:57