Enabling Exploration of CAR T-Cell Design and Integration of Social Justice Context into Chemical Engineering Courses

Prybutok, Alexis Nicole

doi:https://doi.org/10.21985/n2-zcv2-h443

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Enabling Exploration of CAR T-Cell Design and Integration of Social Justice Context into Chemical Engineering Courses

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Chimeric antigen receptor (CAR) T-cell therapies marry advances in cellular engineering with personalized medicine to provide patient-specific, targeted cancer treatments. Though current CAR T-cell therapies successfully target blood cell cancers, treating solid tumors has proven to be more challenging. Solid-tumor CAR designs must overcome several challenges, including tumor microenvironment barriers preventing CAR T-cell infiltration and lack of unique tumor antigens for selective targeting. Given the vast design space and influential tumor context, testing every possible design in vitro or in vivo is prohibitively time-consuming and resource intensive. Thus, there exists a need to efficiently and systematically test designs, understand underlying biological phenomena, and describe emergent behavior. To address this gap, we developed a flight simulator for CAR T-cell therapies: a multi-scale, multi-class agent-based model (ABM)—a “bottom-up” computational model that utilizes first-principles to dictate probabilistic rules that guide agent behaviors and interactions within the context of a local environment—designed to elucidate how inherent tumor features and tunable cell therapy properties affect treatment outcomes. This work builds upon a previously established modeling framework ARCADE (Agent-based Representation of Cells And Dynamic Environments) to include CAR T-cell agents (CAR T-cell ARCADE, or CARCADE). CARCADE integrates the subcellular level details (modules), cell-level decision making (rules), and population-level emergent outcomes (environment and cell interactions). The agents include both cancerous and healthy tissue cells and CD4+ (helper) and CD8+ (cytotoxic) CAR T-cells, where each cell uses modules to manage nutrient uptake and environment sensing. Cells navigate through defined states and rules derived from experimental studies. Using CARCADE, I elucidated how inherent tumor features and tunable therapeutic properties differentially and simultaneously affect treatment outcomes in simulated dish and tissue contexts. CARCADE facilitates deeper biological understanding of treatment design and could ultimately enable identification of promising treatment strategies to accelerate solid tumor CAR T-cell design-build-test cycles.Additionally, I dedicated much of my Ph.D. to engineering education research. Chemical engineering examples and homework problems often lack societal context, specifically failing to connect engineering content, decisions, and designs to diverse groups. Thus, students are rarely given the opportunity to consider the positive or negative impacts of engineering efforts on communities with identities differing from their own. Along with other members of the ChBE Anti-Racism, Diversity, Equity, and Inclusion (ARDEI) Committee, we worked toward integrating ARDEI and social justice contexts into undergraduate and graduate curriculum through homework and example problems. By adding context into our classrooms, we hope to increase inclusivity, awareness of oppressions, and reflection on the intersection of identity and chemical engineering, thereby encouraging critical thinking through an equity lens.

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