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| Item type: | Article | ||||||||||||||||||||||||||||||||||||||||||
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| Journal or Publication Title: | Journal of immunology (Baltimore, Md. : 1950) | ||||||||||||||||||||||||||||||||||||||||||
| Volume: | 170 | ||||||||||||||||||||||||||||||||||||||||||
| Number of Issue or Book Chapter: | 4 | ||||||||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 2161-9 | ||||||||||||||||||||||||||||||||||||||||||
| Date: | 2003 | ||||||||||||||||||||||||||||||||||||||||||
| Institutions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) | ||||||||||||||||||||||||||||||||||||||||||
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| Classification: |
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| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||||||||||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||||||||||||
| Refereed: | Yes, this version has been refereed | ||||||||||||||||||||||||||||||||||||||||||
| Created at the University of Regensburg: | Yes | ||||||||||||||||||||||||||||||||||||||||||
| Item ID: | 14417 |
Abstract
Adoptive T cell therapy has been successfully used for treatment of viral and malignant diseases. However, little is known about the fate and trafficking of transferred Ag-specific T cells. Using the tetramer (TM) technology which allows for detection and quantification of Ag-specific CTL, we assessed the frequency of circulating Melan-A-specific CTL in advanced melanoma patients during adoptive ...
Abstract
Adoptive T cell therapy has been successfully used for treatment of viral and malignant diseases. However, little is known about the fate and trafficking of transferred Ag-specific T cells. Using the tetramer (TM) technology which allows for detection and quantification of Ag-specific CTL, we assessed the frequency of circulating Melan-A-specific CTL in advanced melanoma patients during adoptive T cell therapy. Melan-A-specific CTL were generated from HLA-A2.1(+) patients by in vitro stimulation of CD8(+) T cells with dendritic cells pulsed with a mutated HLA-A2-binding Melan-A (ELAGIGILTV) peptide. Eight patients received three infusions of 0.25-11 x 10(8) Melan-A-specific CTL i.v. at 2-wk intervals along with low-dose IL-2. The transferred T cell product contained a mean of 42.1% Melan-A-TM(+) CTL. Before therapy, the frequencies of Melan-A-specific CTL in patients' circulating CD8(+) T cells ranged from 0.01 to 0.07%. Characterization of the TM frequencies before and at different time points after transfer revealed an increase of circulating Melan-A-specific CTL up to 2%, correlating well with the number of transferred CTL. An elevated frequency of TM(+) T cells was demonstrated up to 14 days after transfer, suggesting long-term survival and/or proliferation of transferred CTL. Combining TM analysis with a flow cytometry-based cytokine secretion assay, unimpaired production of IFN-gamma was demonstrated in vivo for at least 24 h after transfer. Indium-111 labeling of Melan-A-specific CTL demonstrated localization of transferred CTL to metastatic sites as early as 48 h after injection. Overall, the results suggest that in vitro-generated Melan-A-specific CTL survive intact in vivo for several weeks and localize preferentially to tumor.
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