Research Focus: Metabolic programming and bioreactor design for T cell manufacturing.

The antigen-specific behavior of T cells in addition to their proliferative and effector capabilities has resulted in heightened interest pertaining to their therapeutic use. Chimeric Antigen Receptor (CAR)- T cells genetically engineered to target tumor cell antigens have shown unprecedented response rates in several hematological cancers, with currently six FDA-approved therapies on the market. Contrary to conventional biopharmaceuticals and other cancer treatment approaches, CAR-T cell immunotherapy offers the potential of a uniquely adaptable treatment modality.

Despite the success seen in the treatment of B cell malignancies, the use of genetically engineered CAR-T cells in the treatment of multiple myeloma has been associated with a conclusive lack of CAR-T cell persistence. There are many potential causes of the lack of treatment durability, one of which being the onset of T cell exhaustion, a developmental phenomenon resulting from continued antigen-stimulation. Less-differentiated T cells of the stem-like memory (TSCM) and central memory (TCM) phenotype have been shown to result in durable treatment response in hematological cancers including multiple myeloma. My research focus is improving T cell manufacturing, with the goal of maximizing less-differentiated T cell types in the end product. Currently, I aim to do so by using an approach called metabolic programming, which involves influencing the metabolic activity of T cells during the expansion phase of manufacturing, in hopes of biasing them towards specific phenotypes. More specifically, I currently focus on one-carbon metabolism in T cells and its potential influence on T cell differentiation. In addition to metabolic programming, I also actively participate in the research and development of a prototype bioreactor intended for T cell manufacturing. On a day-to-day basis, I primarily run experiments that include T cell expansion and assay optimization.

Relevant Publications:

• Odeh‐Couvertier, V. Y., Dwarshuis, N. J., Colonna, M. B., Levine, B. L., Edison, A. S., Kotanchek, T., Roy K. & Torres‐Garcia, W. (2022). Predicting T‐cell quality during manufacturing through an artificial intelligence‐based integrative multiomics analytical platform. Bioengineering & Translational Medicine, e10282.
• Dwarshuis, N. J., Song, H. W., Patel, A., Kotanchek, T., & Roy, K. (2019). Functionalized microcarriers improve T cell manufacturing by facilitating migratory memory T cell production and increasing CD4/CD8 ratio. bioRxiv, 646760.