Immunometabolic determinants of long-term response in leukemia patients receiving CD19 CAR T cell therapy - PubMed
a day ago
- #Immunometabolism
- #CAR T cell therapy
- #Leukemia
- CD19 CAR T cell therapy shows remission in most relapsed/refractory B-ALL patients, but relapse due to loss of CAR T cell functionality remains a challenge.
- Long-term responders (LTR) exhibit enhanced oxidative phosphorylation, fatty acid oxidation, pentose phosphate pathway activity, higher mitochondrial mass, tighter cristae, and lower mTOR expression in pre-infusion CAR T cells.
- Post-infusion CAR T cells in LTR demonstrate high immunometabolic plasticity and mTOR-pS6 expression, supported by the bone marrow microenvironment.
- Transient mTOR inhibition during CAR T cell manufacturing induces metabolic reprogramming and enhances anti-tumor activity.
- The study provides insights into immunometabolic determinants of long-term response and suggests strategies to improve remission duration.