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Titolo:
Antineoplastic effect of anti-erbB-2 intrabody is not correlated with scFvaffinity for its target
Autore:
Arafat, W; Gomez-Navarro, J; Xiang, JL; Siegal, GP; Alvarez, RD; Curiel, DT;
Indirizzi:
Univ Alabama, Div Human Gene Therapy, Dept Med, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 , Dept Med, Birmingham, AL 35294 USA Univ Alabama, Div Human Gene Therapy, Dept Pathol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ept Pathol, Birmingham, AL 35294 USA Univ Alabama, Div Human Gene Therapy, Dept Surg, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 Dept Surg, Birmingham, AL 35294 USA Univ Alabama, Gene Therapy Ctr, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 herapy Ctr, 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 Surg, Birmingham, AL 35294 USA Univ Alabama BirminghamAL USA 35294 Dept Surg, Birmingham, AL 35294 USA Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 & Gynecol, Birmingham, AL 35294 USA Univ Alexandria, Dept Clin Oncol, Alexandria, Egypt Univ Alexandria Alexandria Egypt ia, Dept Clin Oncol, Alexandria, Egypt
Titolo Testata:
CANCER GENE THERAPY
fascicolo: 9, volume: 7, anno: 2000,
pagine: 1250 - 1256
SICI:
0929-1903(200009)7:9<1250:AEOAII>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
SINGLE-CHAIN ANTIBODY; TUMOR-CELL PROLIFERATION; INTRACELLULAR EXPRESSION; GENE-THERAPY; FV ANTIBODIES; IN-VITRO; CANCER; INHIBITION; DELIVERY; OVARIAN;
Keywords:
gene therapy; single-chain antibody; erbB-2; cytotoxicity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Curiel, DT Univ Alabama, Div Human Gene Therapy, Dept Med, 1824 6th Ave S,Room WTI 620, Birmingham, AL 35294 USA Univ Alabama 1824 6th Ave S,Room WTI620 Birmingham AL USA 35294
Citazione:
W. Arafat et al., "Antineoplastic effect of anti-erbB-2 intrabody is not correlated with scFvaffinity for its target", CANC GENE T, 7(9), 2000, pp. 1250-1256

Abstract

Intracellular single-chain antibodies (scFvs) have emerged as a powerful method to knock out expression of oncoproteins. We have demonstrated previously that scfvs directed against a variety of molecular targets induce specific toxicity in tumor cells. Recently, the utility of an anti-erbB-2 scFv has predicated its evaluation in a phase I gene therapy clinical trial. The utility of scFv as an intrabody is closely linked to its interaction with atarget, Limiting the contribution of the latter to the neoplastic phenotype. In this study, we sought to determine whether improvement in the affinity of the scFv far its cognate target could improve the efficiency of intrabody-mediated oncoprotein knockout. We compared in erbB-2-positive and -negative tumor cells the function of plasmids encoding a newly developed C6.5 anti-erbB-2 scFv, which has a 1000-fold higher affinity, with our original e23 anti-erbB-2 scFv. Intracellular scFv expression, target binding, and tumor cell cytotoxicity were found to be similar in all conditions tested, including dose-response studies with limiting dilutions of the scFv. On this basis, we have concluded that the antineoplastic effect of anti-erbB-2 intrabody is not correlated with scFv affinity for its target.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/06/20 alle ore 06:26:16