Modeling Growth Kinetics of Cytotoxic T Lymphocytes for Cancer Immunotherapy in a High-Density Novel Centrifugal Bioreactor System

Primary author: Brenden Fraser-Hevlin
Co-author(s): Kitana Kaiphanliam; Bernard Van Wie
Faculty sponsor: Dr. Bernard Van Wie

Primary college/unit: Voiland College of Engineering and Architecture
Campus: Pullman

Abstract:

Cancer is the second leading cause of death in the United States and worldwide. Traditional cancer treatments such as chemotherapy, radiation, and surgery are designed to destroy cancer cells but often attack healthy tissue in the process. In immunotherapy, immune cells such as cytotoxic T lymphocytes (CTLs) are extracted, modified, expanded in a bioreactor, and transferred into a patient—this is known as adoptive cell therapy (ACT). There is a need for ACT-based treatments that are widely accessible, scalable, and relatively inexpensive. To address this need, our lab recently developed a high-density, lab-scale centrifugal bioreactor (CBR) which can rapidly expand infected CD8+ T cells from a bovine model. In this study, we aimed to optimize CTL growth by determining kinetic growth parameters based on the levels of glucose and inhibitory metabolites in the culture. It is hypothesized that if we can develop a reliable kinetic growth model, then it will be possible to predict optimal CTL expansion parameters for the bioreactor. Early kinetic studies were performed last fall in which six different glucose concentrations were tested, giving a maximum specific growth rate of 0.0112 1/h and a Monod constant of 2.12 mg glucose/dL. The experiments were repeated recently with different glucose concentrations and the results from those studies will be presented. The optimization of this bioreactor will have a major impact on the availability and efficiency of patient-specific immunotherapy.