PMID: 8938519Oct 1, 1996Paper

Production of human natural killer cells for adoptive immunotherapy using a computer-controlled stirred-tank bioreactor

Journal of Hematotherapy
B A PiersonJ S Miller

Abstract

Large-scale ex vivo expansion of human natural killer (NK) cells for adoptive immunotherapy requires assurance of good manufacturing practices. However, maximal expansion of NK is also desired to facilitate clinical trials with large numbers of IL-2-activated NK (ANK). A closed-system stirred-tank bioreactor is amenable to computer control of culture variables, thereby reducing the risk of contamination. We demonstrate that NK cultured in 250-ml spinner flasks expand 2.5-fold more than NK cultured in stationary tissue culture wells. We further show that during 33 days of culture, it is feasible to control the pH between 7.0 and 7.2 and the dissolved oxygen concentration at 40% of air saturation via direct on-line computer control in a 750-ml stirred-tank bioreactor. On-line measurement of optical density by a laser turbidity sensor, as a measure of cell concentration, correlated well with actual cell count data. NK expansion in the 750-ml bioreactor was 7-fold greater than in stationary tissue culture controls and 3-fold greater than in spinner flask controls. Consumption rates of glucose and oxygen and the production rate of lactate were measured and will be used to develop a nutrient feeding strategy to convert the batch reac...Continue Reading

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Citations

May 17, 2000·Journal of Hematotherapy & Stem Cell Research·L Berkahn
Nov 25, 2000·Journal of Hematotherapy & Stem Cell Research·Y HanazonoC E Dunbar
Aug 31, 2002·Journal of Hematotherapy & Stem Cell Research·Jürgen LuhmChristoph Frohn
Feb 26, 1998·Leukemia & Lymphoma·B A Pierson, J S Miller
Jul 21, 2009·Journal of Internal Medicine·T Sutlu, E Alici
Jun 16, 2010·Cell Proliferation·B ShiM Guo
Feb 27, 2004·Cytotherapy·H-G Klingemann, J Martinson
Nov 10, 2001·Annual Review of Biomedical Engineering·L K Nielsen
Sep 29, 2006·Biotechnology and Bioengineering·Elsa AbranchesJoaquim M S Cabral
Jan 6, 2004·Biotechnology and Bioengineering·Aaron E FosterKenneth F Bradstock
May 12, 2017·Frontiers in Immunology·Markus GranzinEvelyn Ullrich
Apr 27, 2019·Frontiers in Oncology·Shabnum PatelConrad Russell Y Cruz
Apr 15, 2021·Journal of Biological Engineering·Oscar Fabian Garcia-AponteBence Kozma
Apr 2, 1998·Hematology/oncology Clinics of North America·J S Miller

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