Enhancing the metabolic function of CAR T cells for lymphoma

Blood Cancer
Gunjan Shah, MD
Memorial Sloan Kettering Cancer Center


CAR T-cell therapy has changed the treatment paradigms of relapsed diffuse large B-cell lymphoma (DLBCL) by demonstrating long term durability in approximately 40% of treated patients. CAR T-cell therapy is when a patient’s own T-cells (white blood cells that kill cancer cells) are collected via blood draw, then engineered to target specific cancer cells, multiplied, and infused back into the patient. However, the other 60% of patients relapse after CAR T-cell therapy. One challenge facing CAR T-cell therapy is a process called T-cell exhaustion where extended periods of T-cell stimulation results in a loss of their function. Understanding and potentially reversing T-cell exhaustion in patients could potentially improve the effectiveness of CAR T-cell therapy. New research has proposed that sustained T-cell activation generates excessive free radicals which disrupt the metabolic processes required for T-cell proliferation, leading to T-cell exhaustion. The researchers hypothesized that treating the damaged T-cells with an antioxidant, N-acetylcysteine, can reverse the metabolic dysfunction and allow T-cells to regain their function. This phase I study will assess the safety and tolerability of N-acetylcysteine in relapsed/refractory DLBCL patients undergoing treatment with CAR T-cell therapy.

Trial Registration: ClinicalTrials.gov Identifier: NCT05081479