Improved T Cell Function Through Metabolic Modulation Towards an Early-Memory Status Webinar

49:40

Chimeric antigen receptor (CAR) -T cell therapy is a promising immunotherapy due to the ability to rapidly deliver a population of tumor specific T cells. Despite the impressive response rates in patients treated with FDA approved CAR-T cells, not all patients respond to CAR-T therapy. Studies have shown a correlation between central memory T cells and clinical response, whereas T cells from non-responders upregulate genes associated with effector differentiation, glycolysis, and apoptosis. Therefore, elucidating the metabolic requirements that shift T cells toward higher efficacy will allow us to formulate T cell media that foster the production of therapies capable of converting non-responders into responders. One potential strategy to bolster in vivo persistence and efficacy is to “re-program” T cells during ex vivo manufacturing. Tools that will allow us to execute this strategy include our advanced metabolic and proteomic capabilities, a robust T cell expansion medium, and a deep understanding of how the workflow affects the cellular product. We have applied this approach in the development of a new T cell expansion medium that retains a more favorable phenotype, while increasing T cell growth. By combining optimally engineered cells and a “smarter” T cell medium with a fine-tuned workflow, we aim to improve T cell function, even in T cells from patients previously categorized as non-responders.

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