Tyler Simmons (University of Minnesota): Midwest Mathematical Biology Seminar

Zoom Link: https://illinois.zoom.us/j/84907159401?pwd=JboBtq30vntVuEpj8s3yYfAdwlb258.1

Title:  Chemically Self-Assembled Nanorings: Therapeutic Efficacy, Response Variability, and Guiding Principles

Abstract: 

Chemically self-assembled nanorings (CSANs) are next-generation therapeutics targeting various cancers. The nanoring structure, consisting of multiple T cell and tumor cell binding moieties, provides a bispecific facilitation of tumor cell recognition and T cell activation, similar to T cell engager-based therapies (TEs). The novelty of CSANs, beyond the potentially improved avidity compared to TEs, stems from the bispecificity of the multimeric structure derived from monospecific monomers, where deliberate ring dissociation may therefore mitigate the adverse effects of bispecific therapeutics. To better understand and guide CSAN-based therapeutic approaches, we turn to a mathematical perspective.

Mathematical modeling offers a complementary approach to CSAN-based treatment design, enabling real-time insights that inform both the design and interpretation of studies. By simulating treatment dynamics in parallel with laboratory experiments, modeling can elucidate mechanisms of action, predict variability in cellular responses, and guide principles for CSAN construction. This iterative integration of computational and experimental approaches allows each to inform the other, supporting more rational design strategies and ultimately enhancing the likelihood of achieving optimal therapeutic efficacy as CSANs progress toward clinical evaluation.

Presented here is a mathematical framework for CSAN-mediated tumor-immune interactions. This foundational model has been calibrated with preliminary data from CSAN experimentation using T cells from various donors. Key insights derived from this modeling effort portray the preferential binding pathways of current CSAN constructions and suggest that CSAN efficacy may be linked to structural and or physical differences in the CSAN. Additionally, this framework highlights the variability in CSAN efficacy arising from donor-specific T cells, offering predictive guidance on how treatment regimens should be adjusted to overcome this variability.

The Midwest Mathematical Biology Seminar will be a series of virtual talks on mathematical biology featuring speakers from the Midwest region and beyond. All areas of mathematical biology will be represented in the seminar series, and a goal for this seminar is to build connections and foster research collaborations.

More information: https://sites.google.com/view/midwest-mathbio-seminar/home

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