A NOVEL form of CAR T-cell therapy, engineered to enhance immune response, is showing encouraging results in patients with relapsed or refractory lymphoma who previously failed anti-CD19 CAR T-cell treatment. The experimental therapy, huCART19-IL18, combines traditional CAR T cells targeting CD19 with interleukin-18 (IL-18) secretion to boost antitumor activity.
In a first-in-human trial, 21 patients received the engineered cells following a rapid 3-day manufacturing process. Patients were given doses ranging from 3 million to 300 million huCART19-IL18 cells. The treatment demonstrated a manageable safety profile: 62% experienced cytokine release syndrome (mostly mild to moderate), and 14% had mild neurotoxicity. No unexpected side effects were reported.
Early results are promising. At three months post-infusion, 81% of patients had a partial or complete response, including 52% who achieved complete remission. With a median follow-up of 17.5 months, the median duration of response was 9.6 months, with some patients still in remission.
The study, registered under ClinicalTrials.gov number NCT04684563, suggests that huCART19-IL18 may offer renewed hope for patients with few remaining options. By enhancing the immune response with IL-18, this next-generation “armoured” CAR T-cell therapy could represent a major advance in the fight against treatment-resistant B-cell cancers. Further trials will be necessary to confirm its long-term benefits and safety.
Reference
Svoboda J et al. Enhanced CAR T-cell therapy for lymphoma after previous failure. N Engl J Med. 2025;392:1824-35.
