Date: March 1, 2022 @ 4:00PM
Speaker: Dr. W. Gregory Sawyer
Affiliation: Department of Mechanical and Aerospace Engineering, University of Florida
Title: Immuno-Oncology in Three Dimensions: Simulation and Experiments
Abstract: Over the past century, imaging and cell-culture have been locked in a coupled development pipeline limited by the perceived constraints of two-dimensional culture plates, slides, and imaging dishes. The inventions of scanning-confocal microscopy, light-sheet microscopy, and multiphoton microscopy are poised to bring rapid, three-dimensional high-resolution characterization of tissues to medical research once the seemingly intractable problem of maintaining, handling, and working with functional, three-dimensional human microtissue specimens is solved. This presentation outlines a radical new approach to convey human microtissues to medical science and develop multi-organ systems and patient-specific models of disease in an accessible platform optimized for in situ studies of tissue function and dynamics with high-resolution microscopy. We will present in situ measurements of immunotherapy activity in 3D systems of patient derived micro-tumors with expanded cultures of TILs, PBMCs, and CAR T cells. These experiments will follow immune cell migrations, killing, and tumor elimination using in situ scanning confocal microscopy, live-cell imaging techniques, astrophysics inspired AI tracking, spatio-temporal 3D cytokine measurements, and evolutionary dynamics modeling of immunotherapy.
We will describe our first-generation, agent-based simulation code to describe the interactions of car T cells with microtumors and demonstrate its use for one simple case. We have constructed a simple mathematical model to describe this scenario and demonstrate very good agreement between the simulation results and analytic solutions of the model.