(445g) Modeling Growth Kinetics of Cytotoxic T Lymphocytes for Cancer Immunotherapy in a High-Density Centrifugal Bioreactor System

Cancer was the second leading cause of death in the United States and worldwide in 2018. Traditional cancer treatments such as chemotherapy and radiation are designed to destroy cancer cells but often attack healthy tissue in the process. Alternative treatment methods include immunotherapy, which uses a patient’s immune system to fight off cancers. In one form of cancer immunotherapy, known as adoptive cell therapy (ACT), immune cells called cytotoxic T lymphocytes (CTLs) are extracted, modified, rapidly expanded, and transferred into a patient. Current forms of ACT are expensive and inefficient, and there is a need for expansion methods that make ACT-based treatments widely accessible, scalable, and relatively affordable. To address this need, our research group has developed a high-density, lab-scale centrifugal bioreactor (CBR), which can rapidly expand infected CD8+ T cells from a bovine model. In other applications, the CBR has reached cell densities up to 2 x 10⁸ cells per mL in an 11.4 mL chamber over the course of 7 days. In this study, we aimed to optimize CTL growth in the CBR 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 from static culture, 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 h^-1 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 here. In conclusion, optimization of the kinetic growth models for the CBR will have a major impact on the availability and efficiency of patient-specific cancer immunotherapy.