Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?

A phase-I trial of autologous GPC3-targeted CAR T cells armoured with a dominant-negative TGFβ receptor II in 36 patients with hepatocellular carcinoma showed promising initial efficacy, but antigen loss and limited progression-free survival tempered results. The commentary in Nature Reviews Clinical Oncology discusses the remaining barriers—including the immunosuppressive tumour microenvironment and antigen escape—that must be overcome to bring CAR T cell therapy into routine clinical use for solid tumours. The authors highlight that affinity tuning and single-armour strategies may be insufficient and call for combinatorial approaches.