Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells.

By O. Kawalekar, Roddy S. O’Connor, J. Fraietta, Lili Guo, Shannon E. McGettigan, A. Posey, Prachi R Patel, S. Guedan, J. Scholler, B. Keith and 4 more. Immunity, 2016

1,075 citations recorded by the source corpus.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/0e691221e70601bfd277446cd21c385fde229c21

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In Immunology

1. C. June
2. Douglas C. Wallace
3. Wendell A. Lim

In Molecular Biology

1. C. June
2. Douglas C. Wallace
3. Wendell A. Lim
4. M. Beal
5. R. Scarpulla
6. Michael T. Lin

In Oncology

1. C. June
2. Wendell A. Lim
3. Joseph A. Baur
4. Douglas C. Wallace

Citations in the corpus

• Foxp3 reprograms T cell metabolism to function in low glucose high lactate environments (2017, background): “Another approach may be to enhance OXPHOS metabolism in engineered chimeric antigen receptor T cells, which elevates the metabolic robustness of attacking immune cells in the tumor microenvironment (Kawalekar et al., 2016).”
• The Principles of Engineering Immune Cells to Treat Cancer (2017, background): “CAR T cells with CD28 signaling domains have enhanced aerobic glycolysis, while CAR T cells with 4-1BB signaling domains have enhanced mitochondrial biogenesis and increased fatty acid oxidation (Kawalekar et al., 2016).”
• Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma (2017, neutral): “Constipation 31 (31) 31 (31) 0 White-cell count decreased 31 (31) 2 (2) 29 (29)”
• Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses (2018, neutral): “…domains (e.g., CD28 or 4-1BB) is known to have different T cell functions and phenotypes (e.g., T cell differentiation, memory T cell formation) (Kawalekar et al., 2016; Skapenko et al., 2001; Zhu et al., 2007), demonstrating the value of CAR design that allows independent control of different…”
• Recent advances and discoveries on the mechanisms and functions of CAR T cells (2021, neutral): “…difference is not well understood, but previous studies have shown that CD28-based CAR T cells exhibit a more effector-like memory phenotype and have an enhanced glycolytic metabolism, whereas 4-1BB-based CAR T cells have a more central memory phenotype and rely on fatty acid metabolism 54–56 .”
• Metabolic Instruction of Immunity (2017, neutral): “Indeed, modification of the signaling domains within chimeric antigen receptor T cells, used in an alternative form of adoptive cell therapy, with 4-1BB augments mitochondrial biogenesis and oxidative metabolism, enhancing their persistence (Kawalekar et al., 2016).”
• A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma (2017, neutral): “CAR T cells carrying the 4-1BB costimulation domain have been observed to have tonic signaling (42) and increased oxidative phosphorylation (43), which could facilitate the observed engraftment.”
• CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment (2019, background): “(6) found that BBζ CAR T cells had increased mitochondrial spare respiratory capacity (SRC) compared with 28ζ CAR T cells, resulting in greater metabolic efficiency even in nutrient-poor, oxygen depleted conditions such as the TME.”