Early detection and metabolic pathway identification of T cell activation by in-process intracellular mass spectrometry |
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| Institution: | 1. The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA;2. National Science Foundation Engineering Research Center (ERC) for Cell Manufacturing Technologies (CMaT), Atlanta, Georgia, USA;3. Marcus Center for Therapeutic Cell Characterization and Manufacturing, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA;4. The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA;5. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA;1. Unité de thérapie Cellulaire et banque de tissus, Université de Lorraine, CHRU-Nancy, Nancy, France;2. Université de Lorraine, UMR CNRS UL 7365, Campus Santé, Nancy, France;3. Département Méthodologie, Promotion, Investigation, Université de Lorraine, CHRU-Nancy, Nancy, France;4. llogeneic Stem Cell Transplantation Department, Université de Lorraine, CHRU-Nancy, Nancy, France.;5. Flow Cytometry Platform, Batiment de Biologie, Université de Lorraine, CHRU-Nancy, Nancy, France;1. Center for Cellular Engineering, Department of Transfusion Medicine and Center for Cellular Engineering, National Instates of Health Clinical Center, Bethesda, Maryland, USA;2. Department of Medicine (Hematology Division), University of Washington/Fred Hutchinson Cancer Center, Seattle, Washington, USA;1. Department of Radiology, University Hospital, LMU Munich, Munich, Germany;2. Laboratory for Translational Cancer Immunology, Gene Center of the LMU Munich, Munich, Germany;3. German Cancer Consortium (DKTK) and Bavarian Center for Cancer Research (BZKF), partner site Munich, Munich, Germany;4. Department of Medicine III, University Hospital, LMU Munich, Munich, Germany;5. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany;6. Comprehensive Cancer Center München-LMU (CCCMLMU), LMU Munich, Munich, Germany |
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| Abstract: | Background aimsIn-process monitoring and control of biomanufacturing workflows remains a significant challenge in the development, production, and application of cell therapies. New process analytical technologies must be developed to identify and control the critical process parameters that govern ex vivo cell growth and differentiation to ensure consistent and predictable safety, efficacy, and potency of clinical products.MethodsThis study demonstrates a new platform for at-line intracellular analysis of T-cells. Untargeted mass spectrometry analyses via the platform are correlated to conventional methods of T-cell assessment.ResultsSpectral markers and metabolic pathways correlated with T-cell activation and differentiation are detected at early time points via rapid, label-free metabolic measurements from a minimal number of cells as enabled by the platform. This is achieved while reducing the analytical time and resources as compared to conventional methods of T-cell assessment.ConclusionsIn addition to opportunities for fundamental insight into the dynamics of T-cell processes, this work highlights the potential of in-process monitoring and dynamic feedback control strategies via metabolic modulation to drive T-cell activation, proliferation, and differentiation throughout biomanufacturing. |
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