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Titolo:
Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma
Autore:
Dudley, ME; Wunderlich, J; Nishimura, MI; Yu, D; Yang, JC; Topalian, SL; Schwartzentruber, DJ; Hwu, P; Marincola, FM; Sherry, R; Leitman, SF; Rosenberg, SA;
Indirizzi:
NCI, Surg Branch, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892NCI, Surg Branch, NIH, Bethesda, MD 20892 USA NIH, Dept Transfus Med, Bethesda, MD 20892 USA NIH Bethesda MD USA 20892NIH, Dept Transfus Med, Bethesda, MD 20892 USA Univ Chicago, Dept Surg, Sect Gen Surg, Chicago, IL 60637 USA Univ Chicago Chicago IL USA 60637 g, Sect Gen Surg, Chicago, IL 60637 USA
Titolo Testata:
JOURNAL OF IMMUNOTHERAPY
fascicolo: 4, volume: 24, anno: 2001,
pagine: 363 - 373
SICI:
1524-9557(200107/08)24:4<363:ATOCMT>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-INFILTRATING LYMPHOCYTES; CELL CLONES; INTERFERON-GAMMA; IN-VITRO; CD8(+); IMMUNOTHERAPY; VIRUS; INTERLEUKIN-2; EFFICACY; SURVIVAL;
Keywords:
immunotherapy; melanoma; gp100; interleukin-2; T-cell clone;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Dudley, ME NCI, Surg Branch, NIH, Bldg 10,Room 2B-08,9000 Rockville Pike, Bethesda, MD 20892 USA NCI Bldg 10,Room 2B-08,9000 Rockville Pike Bethesda MD USA 20892
Citazione:
M.E. Dudley et al., "Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma", J IMMUNOTH, 24(4), 2001, pp. 363-373

Abstract

This report describes a phase I study of the adoptive transfer of cloned melanoma antigen-specific T lymphocytes for therapy of patients with advanced melanoma. Clones were derived from peripheral blood lymphocytes or tumor-infiltrating lymphocytes of patients who had received prior immunization with the melanoma-associated antigen, gp100. In response to its cognate antigen, each clone used for treatment secreted large amounts of interferon-gamma and granulocyte-macrophage colony-stimulating factor, lesser amounts of interleukin (IL)-2 and tumor necrosis factor-alpha, and little or no IL-4 and IL-10. Clones also demonstrated recognition of human leukocyte antigen-matched melanomas using cytokine secretion and lysis assays. Twelve patients received 2 cycles of cells alone; I I patients received additional cycles of cells and were randomized between two schedules of IL-2 (125,000 IU/kg subcutaneously daily for 12 days versus 720,000 IU/kg intravenously every 8 hfor 4 days). A total of 51 cycles of cells were administered, with an average of 1 x 10(10) cells per cycle. Peripheral blood samples were analyzed for persistence of transferred cells by T-cell receptor-specific polymerase chain reaction. Transferred cells reached a maximum level at I It after transfer but rapidly declined to undetectable levels by 2 weeks. One minor response and one mixed response were observed (both in the high-dose IL-2 arm). This report demonstrates the safety and feasibility of cloned T-cell transfer as a therapy for patients with cancer. The lack of clinical effectiveness of this protocol suggests that transfer of different or additional celltypes or that modulation of the recipient host environment is required forsuccessful therapy.

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Documento generato il 23/01/20 alle ore 13:02:50