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Titolo:
CHIMERIC ZETA-RECEPTORS DIRECT HUMAN NATURAL-KILLER (NK) EFFECTOR FUNCTION TO PERMIT KILLING OF NK-RESISTANT TUMOR-CELLS AND HIV-INFECTED T-LYMPHOCYTES
Autore:
TRAN AC; ZHANG DH; BYRN R; ROBERTS MR;
Indirizzi:
CELL GENESYS,322 LAKESIDE DR FOSTER CITY CA 94404 CELL GENESYS FOSTER CITY CA 94404 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DIV HEMATOL ONCOL BOSTON MA 02215
Titolo Testata:
The Journal of immunology
fascicolo: 2, volume: 155, anno: 1995,
pagine: 1000 - 1009
SICI:
0022-1767(1995)155:2<1000:CZDHN(>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; FC-GAMMA-RIIIA; TYROSINE PHOSPHORYLATION; SOLUBLE CD4; HIGH-AFFINITY; CHAIN; ACTIVATION; INDUCTION; ADHERENCE; STIMULATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
48
Recensione:
Indirizzi per estratti:
Citazione:
A.C. Tran et al., "CHIMERIC ZETA-RECEPTORS DIRECT HUMAN NATURAL-KILLER (NK) EFFECTOR FUNCTION TO PERMIT KILLING OF NK-RESISTANT TUMOR-CELLS AND HIV-INFECTED T-LYMPHOCYTES", The Journal of immunology, 155(2), 1995, pp. 1000-1009

Abstract

Chimeric receptors in which a signaling component of the TCR complex such as zeta is fused directly to the ligand binding domain of a heterologous receptor or Ab have been shown to redirect the specific effector activity of T lymphocytes. We previously described the ability of two classes of such chimeric 5-receptors bearing extracellular domains derived from either the HIV receptor CD4 (CD4 zeta) or an HIV-specificsingle chain Ab to redirect primary human CD8(+) T cells to kill HIV-infected T cells. In this report we demonstrate that human NK cells can be genetically modified to express high levels of CD4 zeta using retroviral transduction. The CD4 zeta chimeric receptor is biochemically active, as cross-linking of CD4 zeta on NK cells results in tyrosine phosphorylation of CD4 zeta and multiple cellular proteins. More importantly, the CD4 zeta chimeric receptor is functionally active and can direct NK cells to specifically and efficiently lyse either NK-resistant tumor cells expressing the relevant ligand, gp120, or CD4(+) T cellsinfected with HIV. These results show that human NK cells can be readily activated via zeta-based chimeric receptors to target both tumor and virally infected cells, and suggest a novel approach to the treatment of disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 01:26:12