Meidenbauer, Norbert and Marienhagen, Joerg and Laumer, Monika and Vogl, Sandra and Heymann, Jana and Andreesen, Reinhard and Mackensen, Andreas (2003) Survival and tumor localization of adoptively transferred Melan-A-specific T cells in melanoma patients. JOURNAL OF IMMUNOLOGY, 170 (4). pp. 2161-2169. ISSN 0022-1767
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PERIPHERAL-BLOOD LYMPHOCYTES; HEMATOPOIETIC PROGENITOR CELLS; I TETRAMERIC COMPLEXES; ALLOGENEIC BONE-MARROW; DENDRITIC CELLS; INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; VITRO STIMULATION; VIRUS INFECTION; IMMUNOTHERAPY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation Medicine > Abteilung für Nuklearmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Sep 2021 06:45 |
| Last Modified: | 20 Sep 2021 06:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39277 |
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