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Titolo:
Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection
Autore:
Walker, RE; Bechtel, CM; Natarajan, V; Baseler, M; Hege, KM; Metcalf, JA; Stevens, R; Hazen, A; Blaese, RM; Chen, CC; Leitman, SF; Palensky, J; Wittes, J; Davey, RT; Falloon, J; Polis, MA; Kovacs, JA; Broad, DF; Levine, BL; Roberts, MR; Masur, H; Lane, HC;
Indirizzi:
NIH, Dept Nucl Med, Bethesda, MD 20892 USA NIH Bethesda MD USA 20892NIH, Dept Nucl Med, Bethesda, MD 20892 USA NIH, Dept Transfus Med, Bethesda, MD 20892 USA NIH Bethesda MD USA 20892NIH, Dept Transfus Med, Bethesda, MD 20892 USA NIH, Dept Crit Care Med, Bethesda, MD 20892 USA NIH Bethesda MD USA 20892NIH, Dept Crit Care Med, Bethesda, MD 20892 USA NIAID, Clin Gene Therapy Branch, Natl Human Genome Res Inst, Clin & Mol Retrovirol Sect,Lab Immunoregulat, Bethesda, MD 20892 USA NIAID Bethesda MD USA 20892 ect,Lab Immunoregulat, Bethesda, MD 20892 USA SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD USA SAIC Frederick MD USA C, Frederick Canc Res & Dev Ctr, Frederick, MD USA Cell Genesys Inc, Foster City, CA USA Cell Genesys Inc Foster City CA USA ell Genesys Inc, Foster City, CA USA Stat Collaborat, Washington, DC USA Stat Collaborat Washington DC USAStat Collaborat, Washington, DC USA Univ Penn, Ctr Canc, Leonard Madlyn Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Res Inst, Philadelphia, PA 19104 USA
Titolo Testata:
BLOOD
fascicolo: 2, volume: 96, anno: 2000,
pagine: 467 - 474
SICI:
0006-4971(20000715)96:2<467:LIVSOR>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
CD28 COSTIMULATION; ADOPTIVE TRANSFER; LYMPHOCYTES-T; RNA LEVELS; IN-VIVO; VIREMIA; INFUSION; AIDS; TRANSDUCTION; INDIVIDUALS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Lane, HC NIH, Dept Nucl Med, Bldg 10,Room 11S231,9000 Rockville, Bethesda,MD 20892USA NIH Bldg 10,Room 11S231,9000 Rockville Bethesda MD USA 20892 2USA
Citazione:
R.E. Walker et al., "Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection", BLOOD, 96(2), 2000, pp. 467-474

Abstract

To study human immunodeficiency virus (HIV)-specific cellular immunity in vivo, we transferred syngeneic lymphocytes after ex vivo expansion and transduction with a chimeric receptor gene (CD4/CD3-zeta) between identical twins discordant for HIV infection. Single and multiple infusions of 10(10) genetically modified CD8(+) T cells resulted in peak fractions in the circulation of approximately 10(4) to 10(5) modified cells/10(6) mononuclear cellsat 24 to 48 hours, followed by 2- to 3-log declines by 8 weeks. In an effort to provide longer high-level persistence of the transferred cells and possibly enhance anti-HIV activity, we administered a second series of infusions in which both CD4(+) and CD8(+) T cells were engineered to express the chimeric receptor and were costimulated ex vivo with beads coated with anti-CDS and anti-CD28. Sustained fractions of approximately 10(3) to 10(4) modified cells/10(6) total CD4(+) or CD8(+) cells persisted for at least 1 year. Assessment of in vivo trafficking of the transferred cells by lymphoid tissue biopsies revealed the presence of modified cells in proportions equivalent to or below those in the circulation. The cell infusions were well tolerated and were not associated with substantive Immunologic or virologic changes. Thus, adoptive transfer of genetically modified HIV-antigen-specific T cells was safe. Sustained survival in the circulation was achieved whenmodified CD4(+) and CD8(+) T cells were infused together after ex vivo costimulation, indicating the important role played by antigen-specific CD4(+)T cells in providing "help" to cytotoxic effecters. (C) 2000 by The American Society of Hematology.

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Documento generato il 05/12/20 alle ore 01:57:05