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Good manufacturing practice production of CD34(+) progenitor-derived NK cells for adoptive immunotherapy in acute myeloid leukemia
Allogeneic natural killer (NK) cell-based immunotherapy is a promising, well-tolerated adjuvant therapeutic approach for acute myeloid leukemia (AML). For reproducible NK cell immunotherapy, a homogenous, pure and scalable NK cell product is preferred. Therefore, we developed a good manufacturing pr...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491545/ https://www.ncbi.nlm.nih.gov/pubmed/37477653 http://dx.doi.org/10.1007/s00262-023-03492-6 |
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author | de Jonge, P. K. J. D. van Hauten, P. M. M. Janssen, L. D. de Goede, A. L. Berrien-Elliott, M. M. van der Meer, J. M. R. Mousset, C. M. Roeven, M. W. H. Foster, M. Blijlevens, N. Hobo, W. Fehniger, T. A. Jansen, J. H. Schaap, N. P. M. Dolstra, H. |
author_facet | de Jonge, P. K. J. D. van Hauten, P. M. M. Janssen, L. D. de Goede, A. L. Berrien-Elliott, M. M. van der Meer, J. M. R. Mousset, C. M. Roeven, M. W. H. Foster, M. Blijlevens, N. Hobo, W. Fehniger, T. A. Jansen, J. H. Schaap, N. P. M. Dolstra, H. |
author_sort | de Jonge, P. K. J. D. |
collection | PubMed |
description | Allogeneic natural killer (NK) cell-based immunotherapy is a promising, well-tolerated adjuvant therapeutic approach for acute myeloid leukemia (AML). For reproducible NK cell immunotherapy, a homogenous, pure and scalable NK cell product is preferred. Therefore, we developed a good manufacturing practice (GMP)-compliant, cytokine-based ex vivo manufacturing process for generating NK cells from CD34(+) hematopoietic stem and progenitor cells (HSPC). This manufacturing process combines amongst others IL15 and IL12 and the aryl hydrocarbon receptor antagonist StemRegenin-1 (SR1) to generate a consistent and active NK cell product that fits the requirements for NK cell immunotherapy well. The cell culture protocol was first optimized to generate NK cells with required expansion and differentiation capacity in GMP-compliant closed system cell culture bags. In addition, phenotype, antitumor potency, proliferative and metabolic capacity were evaluated to characterize the HSPC-NK product. Subsequently, seven batches were manufactured for qualification of the process. All seven runs demonstrated consistent results for proliferation, differentiation and antitumor potency, and preliminary specifications for the investigational medicinal product for early clinical phase trials were set. This GMP-compliant manufacturing process for HSPC-NK cells (named RNK001 cells) is used to produce NK cell batches applied in the clinical trial ‘Infusion of ex vivo-generated allogeneic natural killer cells in combination with subcutaneous IL2 in patients with acute myeloid leukemia’ approved by the Dutch Ethics Committee (EudraCT 2019-001929-27). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-023-03492-6. |
format | Online Article Text |
id | pubmed-10491545 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-104915452023-09-10 Good manufacturing practice production of CD34(+) progenitor-derived NK cells for adoptive immunotherapy in acute myeloid leukemia de Jonge, P. K. J. D. van Hauten, P. M. M. Janssen, L. D. de Goede, A. L. Berrien-Elliott, M. M. van der Meer, J. M. R. Mousset, C. M. Roeven, M. W. H. Foster, M. Blijlevens, N. Hobo, W. Fehniger, T. A. Jansen, J. H. Schaap, N. P. M. Dolstra, H. Cancer Immunol Immunother Research Allogeneic natural killer (NK) cell-based immunotherapy is a promising, well-tolerated adjuvant therapeutic approach for acute myeloid leukemia (AML). For reproducible NK cell immunotherapy, a homogenous, pure and scalable NK cell product is preferred. Therefore, we developed a good manufacturing practice (GMP)-compliant, cytokine-based ex vivo manufacturing process for generating NK cells from CD34(+) hematopoietic stem and progenitor cells (HSPC). This manufacturing process combines amongst others IL15 and IL12 and the aryl hydrocarbon receptor antagonist StemRegenin-1 (SR1) to generate a consistent and active NK cell product that fits the requirements for NK cell immunotherapy well. The cell culture protocol was first optimized to generate NK cells with required expansion and differentiation capacity in GMP-compliant closed system cell culture bags. In addition, phenotype, antitumor potency, proliferative and metabolic capacity were evaluated to characterize the HSPC-NK product. Subsequently, seven batches were manufactured for qualification of the process. All seven runs demonstrated consistent results for proliferation, differentiation and antitumor potency, and preliminary specifications for the investigational medicinal product for early clinical phase trials were set. This GMP-compliant manufacturing process for HSPC-NK cells (named RNK001 cells) is used to produce NK cell batches applied in the clinical trial ‘Infusion of ex vivo-generated allogeneic natural killer cells in combination with subcutaneous IL2 in patients with acute myeloid leukemia’ approved by the Dutch Ethics Committee (EudraCT 2019-001929-27). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-023-03492-6. Springer Berlin Heidelberg 2023-07-21 2023 /pmc/articles/PMC10491545/ /pubmed/37477653 http://dx.doi.org/10.1007/s00262-023-03492-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research de Jonge, P. K. J. D. van Hauten, P. M. M. Janssen, L. D. de Goede, A. L. Berrien-Elliott, M. M. van der Meer, J. M. R. Mousset, C. M. Roeven, M. W. H. Foster, M. Blijlevens, N. Hobo, W. Fehniger, T. A. Jansen, J. H. Schaap, N. P. M. Dolstra, H. Good manufacturing practice production of CD34(+) progenitor-derived NK cells for adoptive immunotherapy in acute myeloid leukemia |
title | Good manufacturing practice production of CD34(+) progenitor-derived NK cells for adoptive immunotherapy in acute myeloid leukemia |
title_full | Good manufacturing practice production of CD34(+) progenitor-derived NK cells for adoptive immunotherapy in acute myeloid leukemia |
title_fullStr | Good manufacturing practice production of CD34(+) progenitor-derived NK cells for adoptive immunotherapy in acute myeloid leukemia |
title_full_unstemmed | Good manufacturing practice production of CD34(+) progenitor-derived NK cells for adoptive immunotherapy in acute myeloid leukemia |
title_short | Good manufacturing practice production of CD34(+) progenitor-derived NK cells for adoptive immunotherapy in acute myeloid leukemia |
title_sort | good manufacturing practice production of cd34(+) progenitor-derived nk cells for adoptive immunotherapy in acute myeloid leukemia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491545/ https://www.ncbi.nlm.nih.gov/pubmed/37477653 http://dx.doi.org/10.1007/s00262-023-03492-6 |
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