Advancing T Cell Mediated Therapy Using 3D Tumor Organoids and Microfluidics

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.