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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
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.
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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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