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Titolo:
Prolonged survival and tissue trafficking following adoptive transfer of CD4 zeta gene-modified autologous CD4(+) and CD8(+) T cells in human immunodeficiency virus-infected subjects
Autore:
Mitsuyasu, RT; Anton, PA; Deeks, SG; Scadden, DT; Connick, E; Downs, MT; Bakker, A; Roberts, MR; June, CH; Jalali, S; Lin, AA; Pennathur-Das, R; Hege, KM;
Indirizzi:
Cell Genesys Inc, Foster City, CA 94404 USA Cell Genesys Inc Foster City CA USA 94404 Inc, Foster City, CA 94404 USA Univ Calif Los Angeles, Los Angeles, CA 90024 USA Univ Calif Los Angeles Los Angeles CA USA 90024 Los Angeles, CA 90024 USA San Francisco Gen Hosp, San Francisco, CA 94110 USA San Francisco Gen Hosp San Francisco CA USA 94110 Francisco, CA 94110 USA Massachusetts Gen Hosp, Boston, MA 02114 USA Massachusetts Gen Hosp Boston MA USA 02114 Gen Hosp, Boston, MA 02114 USA Univ Colorado, Hlth Sci Ctr, Denver, CO USA Univ Colorado Denver CO USAUniv Colorado, Hlth Sci Ctr, Denver, CO USA Stat Collaborat, Washington, DC USA Stat Collaborat Washington DC USAStat Collaborat, Washington, DC USA Specialty Labs, Los Angeles, CA USA Specialty Labs Los Angeles CA USASpecialty Labs, Los Angeles, CA USA Univ Virginia, Charlottesville, VA 22903 USA Univ Virginia Charlottesville VA USA 22903 Charlottesville, VA 22903 USA Univ Penn, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104Univ Penn, Philadelphia, PA 19104 USA
Titolo Testata:
BLOOD
fascicolo: 3, volume: 96, anno: 2000,
pagine: 785 - 793
SICI:
0006-4971(20000801)96:3<785:PSATTF>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
EPSTEIN-BARR-VIRUS; ALLOGENEIC BONE-MARROW; CLASS-I MOLECULES; HIV-1 INFECTION; LYMPHOCYTE RESPONSES; DISEASE PROGRESSION; CD28 COSTIMULATION; VIRAL REPLICATION; VIVO; IMMUNITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Hege, KM Cell Genesys Inc, 342 Lakeside Dr, Foster City, CA 94404 USA CellGenesys Inc 342 Lakeside Dr Foster City CA USA 94404 404 USA
Citazione:
R.T. Mitsuyasu et al., "Prolonged survival and tissue trafficking following adoptive transfer of CD4 zeta gene-modified autologous CD4(+) and CD8(+) T cells in human immunodeficiency virus-infected subjects", BLOOD, 96(3), 2000, pp. 785-793

Abstract

We have genetically engineered CD4(+) acid CD8(+) T cells with human immunodeficiency Virus (HIV) specificity by Inserting a gene, CD4 zeta, containing the extracellular domain of human CD4 (which binds HIV env) linked to the zeta (zeta) chain of the T-cell receptor (which mediates T-cell activation), Twenty-four HIV-positive subjects received a single infusion of 2 to 3 x 10(10) autologous CD4 zeta-modified CD4(+) and CD8+ T cells administered with (n = II) or without (n = 13) Interleukin-2 (IL-2), Subjects had CD4 counts greater than 50/mu L and viral loads of at least 1000 copies/ml at entry. T cells were costimulated ex vivo through CD3 and CD28 and expanded forapproximately 2 weeks, CD4 zeta was detected in 1% to 3% of blood mononuclear cells at 8 weeks and 0.1% at 1 year after infusion, and survival was not enhanced by IL-2. Trafficking of gene-modified T cells to bulk rectal tissue and/or isolated lamina propria lymphocytes was documented in a subset of 5 of 5 patients at 14 days and 2 of 3 at 1 year. A greater than 0.5 log mean decrease in rectal tissue-associated HIV RNA was observed for at least Iri days, suggesting compartmental antiviral activity of CD4 zeta T cells. CD4+ counts increased by 73/mu L at 8 weeks in the group receiving IL-2, There was no significant mean change in plasma HIV RNA or blood proviral DNA in either treatment arm. This sustained, high-level persistence of gene-modified T cells demonstrates the feasibility of ex vivo T-cell gene therapy in HIV-infected adults and suggests the importance of providing HIV-specificT-helper function. (C) 2000 by The American Society of Hematology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 00:50:16