BACKGROUND AIMS: Natural killer (NK) cell-based adoptive immunotherapy is a promising approach for the treatment of cancer. Ex vivo expansion and activation of NK cells under good manufacturing practice (GMP) conditions are crucial for facilitating large clinical trials. The goal of this study was to optimize a large-scale, feeder-free, closed system for efficient NK cell expansion. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy donors and myeloma patients were cultured for 21 days using flasks, cell culture bags and bioreactors. Final products from different expansions were evaluated comparatively for phenotype and functionality. RESULTS: Significant NK cell expansions were obtained in all systems. The bioreactor yielded a final product rich in NK cells (mean 38%) ensuring that a clinically relevant cell dose was reached (mean 9.8 x 10⁹ NK cells). Moreover, we observed that NK cells expanded in the bioreactor displayed significantly higher cytotoxic capacity. It was possible to attribute this partially to a higher expression level of NKp44 compared with NK cells expanded in flasks. CONCLUSIONS: These results demonstrate that large amounts of highly active NK cells for adoptive immunotherapy can be produced in a closed, automated, large-scale bioreactor under feeder-free current GMP conditions, facilitating clinical trials for the use of these cells.
BACKGROUND AIMS: Natural killer (NK) cell-based adoptive immunotherapy is a promising approach for the treatment of cancer. Ex vivo expansion and activation of NK cells under good manufacturing practice (GMP) conditions are crucial for facilitating large clinical trials. The goal of this study was to optimize a large-scale, feeder-free, closed system for efficient NK cell expansion. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy donors and myelomapatients were cultured for 21 days using flasks, cell culture bags and bioreactors. Final products from different expansions were evaluated comparatively for phenotype and functionality. RESULTS: Significant NK cell expansions were obtained in all systems. The bioreactor yielded a final product rich in NK cells (mean 38%) ensuring that a clinically relevant cell dose was reached (mean 9.8 x 10⁹ NK cells). Moreover, we observed that NK cells expanded in the bioreactor displayed significantly higher cytotoxic capacity. It was possible to attribute this partially to a higher expression level of NKp44 compared with NK cells expanded in flasks. CONCLUSIONS: These results demonstrate that large amounts of highly active NK cells for adoptive immunotherapy can be produced in a closed, automated, large-scale bioreactor under feeder-free current GMP conditions, facilitating clinical trials for the use of these cells.
Authors: Yuk Pheel Park; Seung-Chul Choi; Patricia Kiesler; Aleksandra Gil-Krzewska; Francisco Borrego; Jennifer Weck; Konrad Krzewski; John E Coligan Journal: Blood Date: 2011-08-03 Impact factor: 22.113
Authors: Stefan O Ciurea; Jolie R Schafer; Roland Bassett; Cecele J Denman; Kai Cao; Dana Willis; Gabriela Rondon; Julianne Chen; Doris Soebbing; Indreshpal Kaur; Alison Gulbis; Sairah Ahmed; Katayoun Rezvani; Elizabeth J Shpall; Dean A Lee; Richard E Champlin Journal: Blood Date: 2017-08-23 Impact factor: 22.113
Authors: Natalia Lapteva; April G Durett; Jiali Sun; Lisa A Rollins; Leslie L Huye; Jian Fang; Varada Dandekar; Zhuyong Mei; Kimberley Jackson; Juan Vera; Jun Ando; Minhtran C Ngo; Elaine Coustan-Smith; Dario Campana; Susann Szmania; Tarun Garg; Amberly Moreno-Bost; Frits Vanrhee; Adrian P Gee; Cliona M Rooney Journal: Cytotherapy Date: 2012-08-17 Impact factor: 5.414