Metabolic reprogramming to optimize the cellular fitness and function of engineered T cells
Immunology, Medicine, Immunometabolism
Metabolic reprogramming is a hallmark of immune cell activation. Key metabolic pathways such as glycolysis, oxidative phosphorylation and lipolysis not only provide energy and building blocks for the synthesis of macromolecules but are also pivotal regulators of the fate and fitness of immune cells. Thus, engineering metabolic pathways of lymphocytes including chimeric antigen receptor (CAR)-expressing T cells represents a promising strategy to augment and optimize immune cell function for therapeutic purposes.
e.g. in obesity and diabetes, shape the composition and functionality of cytotoxic lymphocytes subsets. Therefore, we will systematically explore the expression profiles of metabolic enzymes and transporters (METs) and the metabolic phenotype of different murine and human lymphocyte subsets as well as CAR T cells with regard to metabolic pathologies of the host. Functional characterization of selected METs in murine and human (CAR)
T cells will identify novel molecular targets for advanced metabolic T cell engineering using CRISPR/Cas9-mediated genome editing and ectopic overexpression strategies.
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