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Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients
BACKGROUND: Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL), in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleuki...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514199/ https://www.ncbi.nlm.nih.gov/pubmed/22909342 http://dx.doi.org/10.1186/1479-5876-10-169 |
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author | Ellebaek, Eva Iversen, Trine Zeeberg Junker, Niels Donia, Marco Engell-Noerregaard, Lotte Met, Özcan Hölmich, Lisbet Rosenkrantz Andersen, Rikke Sick Hadrup, Sine Reker Andersen, Mads Hald thor Straten, Per Svane, Inge Marie |
author_facet | Ellebaek, Eva Iversen, Trine Zeeberg Junker, Niels Donia, Marco Engell-Noerregaard, Lotte Met, Özcan Hölmich, Lisbet Rosenkrantz Andersen, Rikke Sick Hadrup, Sine Reker Andersen, Mads Hald thor Straten, Per Svane, Inge Marie |
author_sort | Ellebaek, Eva |
collection | PubMed |
description | BACKGROUND: Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL), in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL)-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections. METHODS: This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625) including patients with metastatic melanoma, PS ≤1, age <70, measurable and progressive disease and no involvement of the central nervous system. Six patients were treated with lymphodepleting chemotherapy, TIL infusion, and 14 days of subcutaneous low-dose IL-2 injections, 2 MIU/day. RESULTS: Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3–4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months), 2 patients had stable disease (4 and 5 months) and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission. CONCLUSION: Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy. |
format | Online Article Text |
id | pubmed-3514199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35141992012-12-05 Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients Ellebaek, Eva Iversen, Trine Zeeberg Junker, Niels Donia, Marco Engell-Noerregaard, Lotte Met, Özcan Hölmich, Lisbet Rosenkrantz Andersen, Rikke Sick Hadrup, Sine Reker Andersen, Mads Hald thor Straten, Per Svane, Inge Marie J Transl Med Research BACKGROUND: Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL), in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL)-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections. METHODS: This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625) including patients with metastatic melanoma, PS ≤1, age <70, measurable and progressive disease and no involvement of the central nervous system. Six patients were treated with lymphodepleting chemotherapy, TIL infusion, and 14 days of subcutaneous low-dose IL-2 injections, 2 MIU/day. RESULTS: Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3–4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months), 2 patients had stable disease (4 and 5 months) and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission. CONCLUSION: Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy. BioMed Central 2012-08-21 /pmc/articles/PMC3514199/ /pubmed/22909342 http://dx.doi.org/10.1186/1479-5876-10-169 Text en Copyright ©2012 Ellebaek et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Ellebaek, Eva Iversen, Trine Zeeberg Junker, Niels Donia, Marco Engell-Noerregaard, Lotte Met, Özcan Hölmich, Lisbet Rosenkrantz Andersen, Rikke Sick Hadrup, Sine Reker Andersen, Mads Hald thor Straten, Per Svane, Inge Marie Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients |
title | Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients |
title_full | Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients |
title_fullStr | Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients |
title_full_unstemmed | Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients |
title_short | Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients |
title_sort | adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose interleukin-2 in metastatic melanoma patients |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514199/ https://www.ncbi.nlm.nih.gov/pubmed/22909342 http://dx.doi.org/10.1186/1479-5876-10-169 |
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