(277a) Rapid Expansion of Cytotoxic T Lymphocytes in a Centrifugal Bioreactor with Applications in Cancer Immunotherapy

Adoptive cell therapy (ACT) has proven to be a promising form of cancer treatment; however, it lacks accessibility due to current expansion techniques. ACT requires rapid expansion of high-density cell cultures in vitro prior to patient administration, and depending on the stage of cancer, the patient may be required to go through multiple treatments. To address this high cell demand, researchers at Washington State University have developed a novel centrifugal bioreactor (CBR), which has been utilized for a number of applications. The CBR operates in perfusion at high centrifugal forces, while the cells are continuously fed with fresh medium. The balance of forces along with nutrient maintenance has allowed us to reach densities of 10⁸ cells/mL. To further study the CBR for immunotherapy purposes, we are rapidly expanding cytotoxic T lymphocytes (CTLs) from a bovine system; cattle produce a similar immune response to that of cancer patients when affected by the Theileria parva parasite. In order to optimize cell growth in the reactor, we are producing a kinetic model to understand how the cells respond to environmental changes when consuming nutrients and producing toxic metabolites such as ammonium ion and lactic acid. Another point of interest for this project is in utilizing some form of biotin-streptavidin-based anti-CD3 support to enhance cell activation and proliferation before and during cultivation in the CBR. The results of these studies will be presented at the annual AIChE meeting.