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T-cells are what they eat metabolic strategies to enhance car t-cell function and persistence Caitlin Hopkins
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Hopkins, Caitlin, author.
- Language:
- English
- Subjects (All):
- Immunology.
- Oncology.
- Cellular biology.
- 0982.
- 0992.
- 0379.
- Local Subjects:
- Immunology.
- Oncology.
- Cellular biology.
- 0982.
- 0992.
- 0379.
- Genre:
- Academic theses
- Physical Description:
- 1 online resource (157 pages)
- Contained In:
- Dissertations Abstracts International 87-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2026
- Language Note:
- English
- Summary:
- Metabolic signaling is a major determinant of T-cell activation, differentiation, and persistence, but the metabolic programs that determine durable clinical CAR T-cell responses are incompletely understood. This thesis investigates the impact of metabolic signaling during CAR T-cell ex vivo manufacturing to understand how nutrient availability shapes cell state to enable durable functional persistence in patients. Integrating controlled manufacturing changes with longitudinal clinical outcomes and mechanistic profiling revealed that a metabolic environment driving glutamine catabolism, cholesterol biosynthetic programs, and NF-kB signaling confers a highly activated cell state primed for antigen independent persistence. This metabolic conditioning promoted durable functional persistence in patients, demonstrating that metabolic programming underpins long-term responses in the clinic. Therefore, a strategy to reshape a metabolic pathway linked to epigenetic reprogramming was investigated. Genetic targeting of the enzyme, L2HGDH, alters a metabolic program and induces enhanced proliferation and function in vitro, but not in vivo. Together, these findings highlight the complexity of metabolic signaling in T-cell biology and reveal metabolic determinants of long-term CAR T-cell functional efficacy
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
- Advisors: Fraietta, Joseph A. Committee members: Kohli, Rahul; Carreno, Beatriz M.; Bhoj, Vijay G.; O'Connor, Roddy
- Ph.D. University of Pennsylvania 2026
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798247972846
- Access Restriction:
- Restricted for use by site license
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