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Titolo:
Functional expression of chimeric receptor genes in human T cells
Autore:
Eshhar, Z; Waks, T; Bendavid, A; Schindler, DG;
Indirizzi:
Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 unol, IL-76100 Rehovot, Israel
Titolo Testata:
JOURNAL OF IMMUNOLOGICAL METHODS
fascicolo: 1-2, volume: 248, anno: 2001,
pagine: 67 - 76
SICI:
0022-1759(20010201)248:1-2<67:FEOCRG>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
GREEN FLUORESCENT PROTEIN; PERIPHERAL-BLOOD LYMPHOCYTES; RETROVIRAL VECTORS; SINGLE-CHAIN; FIBRONECTIN FRAGMENTS; LEUKEMIA-VIRUS; TARGET-CELLS; IN-VIVO; TRANSDUCTION; IMMUNOGLOBULIN;
Keywords:
chimeric receptor; retrovectors; T cells; gene expression; gene delivery;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Eshhar, Z Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 6100 Rehovot, Israel
Citazione:
Z. Eshhar et al., "Functional expression of chimeric receptor genes in human T cells", J IMMUNOL M, 248(1-2), 2001, pp. 67-76

Abstract

Tumor immunotherapy has been limited to date by the poor antigenicity of most tumors, the immunocompromised state of many cancer patients, and the slow tumor penetration and short half-life of exogenously-introduced anti-tumor antibodies. Our group has developed a model immunotherapy system using achimeric construct containing an antibody V region fused to a T cell activation molecule (T body) introduced by transfection into cytotoxic T cell lines, or populations of activated primary T or natural killer (NK) cells, Inthis study we have optimized the conditions needed for efficient transduction of human peripheral lymphocytes (PBL) using retroviral vectors pseudotyped with the gibbon ape leukemia virus (GaLV) envelope. Selection of packaging cells producing high virus titers was performed following transfection with constructs containing the green fluorescent protein (GFP), and FAGS sorting. As a model chimeric receptor gene we used a tripartite construct consisting of a single-chain anti-TNP antibody variable region linked to part of the extracellular domain and the membrane spanning regions of the CD28 coreceptor molecule and joined at its 5' end to a gene fragment encoding theintracellular moiety of the gamma activation molecule common to the Fc epsilon and Fc gamma receptors. Enriched preparations of retrovectors containing this chimeric receptor and the GFP gene could stably and efficiently transduce human PBL co-activated by anti-CD3 and anti-CD28 antibodies. In routine experiments, the transgene was expressed in 35-70% of the human T cells. Such lymphocytes express the chimeric receptors on their surface and uponstimulation with hapten immobilized on plastic they can produce IL-2. Transfectomas activated in this manner also undergo specific proliferation in the absence of exogenous IL-2. Moreover, the transduced lymphocytes could effectively lyse target cells expressing the TNP hapten on their surface. These studies establish the conditions for the optimal transfection of effector lymphocytes to redirect them against a variety of tumor targets. (C) 2001Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 22:51:52