Novel xeno-free and serum-free culturing condition to improve piggyBac transposon-based CD19 chimeric antigen receptor T-cell production and characteristics |
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| Affiliation: | 1. Medical Microbiology, Interdisciplinary and International Program, Graduate School, Chulalongkorn University, Bangkok, Thailand;2. Cellular Immunotherapy Research Unit, Chulalongkorn University, Bangkok, Thailand;3. Chulalongkorn Comprehensive Cancer Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand;4. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand;5. Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan;6. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan;7. Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;8. Department of Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;1. Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Takamatsu, Japan;2. Department of Hematology, Takamatsu Red Cross Hospital, Takamatsu, Japan;3. Department of Hematology, Kagawa Prefectural Central Hospital, Takamatsu, Japan;1. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;2. Immunologic Monitoring & Cellular Products Laboratory, University of Pittsburgh Hillman Cancer Center, Pittsburgh, Pennsylvania, USA;3. Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;4. Department of Medicine, Division of Hematology and Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA;5. Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;1. Universidad San Francisco de Quito USFQ, Colegio de Ciencias de la Salud, Escuela de Medicina, Quito, Ecuador;2. Universidad San Francisco de Quito USFQ, Instituto de Investigaciones en Biomedicina iBioMed, Quito, Ecuador;3. Mito-Act Research Consortium, Quito, Ecuador;4. Sistemas Médicos SIME, Universidad San Francisco de Quito USFQ, Quito, Ecuador;5. Biología, Colegio de Ciencias Biológicas y Ambientales COCIBA, Universidad San Francisco de Quito USFQ, Quito, Ecuador;6. Instituto de investigaciones biotecnológicas IIB, Universidad Nacional de San Martín, Buenos Aires, Argentina;7. School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands;8. Instituto de Neurociencias, Universidad San Francisco de Quito USFQ, Quito, Ecuador;9. Fundação Oswaldo Cruz, FIOCRUZ Instituto Oswaldo Cruz (IOC), Rio de Janeiro, Brazil;1. IdiPAZ, Hospital La Paz Institute for Health Research, La Paz University Hospital, Madrid, Spain;2. Biostatistics Department, La Paz University Hospital, Madrid, Spain;3. Histocompatibility Unit, Transfusion Center of Madrid, Madrid, Spain;4. Cell Therapy Unit, Hematology Department, La Paz University Hospital, Madrid, Spain;5. Pediatric Hemato-oncology Department, La Paz University Hospital, Madrid, Spain;6. Faculty of Medicine Autonomous, University of Madrid, Madrid, Spain;1. Department of Molecular Medicine, UF Scripps Biomedical Research, Jupiter, FL, USA;2. Hematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy;1. Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA;2. Department of Kinesiology and Health Education, University of Texas at Austin, Austin, Texas, USA |
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| Abstract: | Background aimsChimeric antigen receptor (CAR) T cell is a novel therapy for relapse and refractory hematologic malignancy. Characteristics of CAR T cells are associated with clinical efficacy and toxicity. The type of serum supplements used during cultivation affects the immunophenotype and function of viral-based CAR T cells. This study explores the effect of serum supplements on nonviral piggyBac transposon CAR T-cell production.MethodsPiggyBac CD19 CAR T cells were expanded in cultured conditions containing fetal bovine serum, human AB serum or xeno-free serum replacement. We evaluated the effect of different serum supplements on cell expansion, transduction efficiency, immunophenotypes and antitumor activity.ResultsXeno-free serum replacement exhibited comparable CAR surface expression, cell expansion and short-term antitumor activity compared with conventional serum supplements. However, CAR T cells cultivated with xeno-free serum replacement exhibited an increased naïve/stem cell memory population and better T-cell expansion after long-term co-culture as well as during the tumor rechallenge assay.ConclusionsOur study supports the usage of xeno-free serum replacement as an alternative source of serum supplements for piggyBac-based CAR T-cell expansion. |
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