Three‑year‑old enters complete remission of hepatoblastoma after experimental GPC3‑CAR T therapy

A three-year-old boy in the United States has gone into complete remission from an aggressive liver cancer, hepatoblastoma, after receiving an experimental CAR T‑cell immunotherapy that targets glypican‑3 (GPC3). Physicians report that the outcome — disappearance of metastatic disease after only two outpatient infusions — provides fresh hope for treating some solid tumours in children.

Clinical context and prior treatment

At diagnosis the primary liver mass in the boy’s left lobe measured 11.2 x 9.6 x 7.1 centimetres. The cancer had spread to the lungs and there were concerns about possible bone involvement. Before enrolling in the trial he had already undergone three cycles of chemotherapy and surgical removal of the primary tumour, followed by two operations to excise pulmonary metastases; despite these interventions the disease recurred and a new lesion appeared in the lungs.

As a participant in a first‑in‑human Phase 1 trial called CARE, he received a specialised form of CAR T‑cell therapy engineered to recognise glypican‑3 (GPC3), a protein highly expressed on liver tumours. Investigators also equipped the modified T cells with genes encoding interleukin‑15 and interleukin‑21, based on preclinical data suggesting those cytokines can extend CAR T‑cell survival and enhance tumour killing.

After the first infusion imaging showed a partial response and blood tumour markers fell. Eight weeks later the child received a second infusion. Subsequent scans revealed no remaining signs of cancer aside from residual scarring, and more than one year after therapy he remained free of detectable disease. The authors report the complete disappearance of metastatic liver cancer following only two ambulatory infusions, with no serious adverse events or systemic toxicity reported.

Researchers stress that this is a single‑patient result from an early‑phase trial and that larger studies and longer follow‑up are required to confirm safety and efficacy. The CARE study is conducted at Baylor College of Medicine; a parallel trial called IMPACT is underway at Seattle Children’s Hospital. The case was described in The New England Journal of Medicine.

Historically, CAR T‑cell therapy has achieved its greatest successes against blood cancers rather than solid tumours. Investigators say factors that may have helped here include the relatively small tumour burden at relapse and the pulmonary location of the recurrence, where intravenously infused CAR T cells first travel and can exert antitumour effects while limiting systemic toxicity. The study team suggests that 15.21.GPC3‑CAR T cells warrant further evaluation as a potential safe and effective treatment for GPC3‑positive hepatoblastoma and other solid tumours.

Photo: press material from the event