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Titolo:
TARGETED ADENOVIRUS-MEDIATED GENE DELIVERY TO T-CELLS VIA CD3
Autore:
WICKHAM TJ; LEE GM; TITUS JA; SCONOCCHIA G; BAKACS T; KOVESDI I; SEGAL DM;
Indirizzi:
GENVEC INC ROCKVILLE MD 20852 NCI,EXPT IMMUNOL BRANCH BETHESDA MD 20892 NATL INST ONCOL,DEPT IMMUNOL BUDAPEST HUNGARY
Titolo Testata:
Journal of virology
fascicolo: 10, volume: 71, anno: 1997,
pagine: 7663 - 7669
SICI:
0022-538X(1997)71:10<7663:TAGDTT>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERIPHERAL-BLOOD LYMPHOCYTES; PENTON BASE; RECEPTOR; EXPRESSION; ATTACHMENT; INFECTION; INTEGRIN; BINDING; COMPLEX; THERAPY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
T.J. Wickham et al., "TARGETED ADENOVIRUS-MEDIATED GENE DELIVERY TO T-CELLS VIA CD3", Journal of virology, 71(10), 1997, pp. 7663-7669

Abstract

T cells are primary targets in numerous gene therapy protocols. However, the use of subgroup C adenovirus serotype 2 or 5 (Ad2 or Ad5) as avector to transduce T cells is limited by its poor transduction efficiency for these cells. In this report we show that poor T-cell transduction results from these cells lacking both the primary Ad2-Ad5 receptor, used in attachment, and the secondary Ad receptor, which mediates entry of most adenovirus serotypes. These deficiencies,were overcome by using a bispecific antibody (bsAb) with specificities for human CD3 and for a FLAG epitope genetically introduced into Ad5 (Ad,FLAG) to redirect the virus to human T cells, The anti-FLAG x anti-CD3 bsAb increased Ad,FLAG binding 30-fold, induced the efficient uptake of Ad.FLAG into the cells? and led to a 100- to 500-fold increase in the transduction of resting T cells. Moreover, fluorescence-activated cell sorter analysis showed that 25 to 90% of the T cells were transduced by the bsAb-complexed Ad,FLAG at multiplicities of infection between 20 and 100 active particles per cell, These results demonstrate that bsAbs can target Ad to non-Ad receptors on cells that are normally resistant to Ad, resulting in their efficient and specific transduction.

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Documento generato il 10/07/20 alle ore 02:20:35