Advancing T Cell Mediated Therapy Using 3D Tumor Organoids and Microfluidics
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- abstract
- Cancer is one of the most common leading causes of fatality in the world, with around 600,000 deaths per year. The adaptive immune system plays a major role in eliminating and preventing further growth of invading entities. T cells are a major component of this system that are trained to recognize antigens through antigen presenting cells (APCs). APC’s give the T cells information needed to proliferate and destroy target cells, eliciting an immune response. For the body to fight cancer on its own, a large amount of T cells, as well as persistent activation of T cells is needed. Naturally occurring T cells typically do not have these qualities; therefore, immunotherapy is a helpful treatment designed to enhance the immune system to fight cancer, while limiting additional cytotoxicity to the body.In this work we aimed to recapitulate the adaptive immune system on a microfluidic chip. The proposed system circulates patient-derived T cells around immune enhanced organoids to allow the T cells time to interact and become familiar with the tumor cells they need to attack. Once the T cells gain exposure to immune enhanced organoids, they are expanded to produce familiarized T cells in abundance. We hypothesize that circulated and expanded T cells will have an enhanced recognition and cytotoxic activity when they are re-introduced to the tumor cells. Initial evidence suggests that ex vivo circulation of immune cells with 3D tumor organoids may educate the T cells to recognize and attack the tumor cells. Continuing work will determine the potential of our approach as a tool for improving personalized immunotherapy.
- subject
- adaptive immunity
- cancer
- immunotherapy
- microfluidics
- organoid
- T cells
- contributor
- Hall, Adam R (committee chair)
- Soker, Shay (committee member)
- Yazdani, Saami K (committee member)
- date
- 2022-05-24T08:36:11Z (accessioned)
- 2022-05-24T08:36:11Z (available)
- 2022 (issued)
- degree
- Biomedical Engineering (discipline)
- identifier
- http://hdl.handle.net/10339/100769 (uri)
- language
- en (iso)
- publisher
- Wake Forest University
- title
- Advancing T Cell Mediated Therapy Using 3D Tumor Organoids and Microfluidics
- type
- Thesis