Abstract
The adoptive transfer of the chimeric antigen receptor (CAR) expressing T-cells has produced unprecedented successful results in the treatment of B-cell malignancies. However, the use of this technology in other malignancies remains less effective. In the setting of solid neoplasms, CAR T-cell metabolic fitness needs to be optimal to reach the tumor and execute their cytolytic function in an environment often hostile. It is now well established that both tumor and T cell metabolisms play critical roles in controlling the immune response by conditioning the tumor microenvironment and the fate and activity of the T cells. In this review, after a brief description of the tumoral and T cell metabolic reprogramming, we summarize the latest advances and new strategies that have been developed to improve the metabolic fitness and efficacy of CAR T-cell products.
Highlights
Chimeric Antigen Receptor (CAR) T-cells are T lymphocytes that have been engineered to target malignant cells [1]
The therapeutic successes obtained with CAR T-cells, followed by the approval from the American and European medicines regulatory agencies (Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively) of two CAR T-cell products targeting the CD19 antigen for the treatment of pediatric/young adult B-cell acute lymphoblastic leukemia (Kymriah®) and adult large B-cell lymphoma (Yescarta®) [3,4], are the results of many years of research mainly based on the understanding of T cell biology and of their interaction with the surrounding environment [5,6]
After a brief description of metabolic reprogramming of the tumors and T cells, we summarize the latest advances and new strategies that are proposed to improve the metabolic fitness and the anti-tumor activity of CAR T-cells
Summary
Chimeric Antigen Receptor (CAR) T-cells are T lymphocytes that have been engineered to target malignant cells [1]. CARs are synthetic molecules designed to activate T cells in response to a specific antigen, mimicking T cell activation through the T cell receptor (TCR) and associated costimulatory molecules. Emerging evidence indicates that the metabolism is a key factor in driving the immune response by regulating the activity and the fate of the T cells. From their naïve to highly differentiated effector function, T cells undergo metabolic reprogramming [7]. CAR T-cells are designed to target an antigen on the surface of cells and they need to be metabolically fit to reach the tumor, survive in an immunosuppressive microenvironment and display their cytolytic function [13]. After a brief description of metabolic reprogramming of the tumors and T cells, we summarize the latest advances and new strategies that are proposed to improve the metabolic fitness and the anti-tumor activity of CAR T-cells
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