CAR T cells show efficacy in advanced liver cancer trial
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A Nature study published July 15 reports that GPC3-specific CAR T cells armored with a dominant-negative TGFβ receptor II showed enhanced efficacy and tolerable safety in 12 patients with advanced hepatocellular carcinoma. All patients had developed resistance or not responded to prior therapy. The trial marks a step forward for solid tumor CAR T therapy.
The Trial Design
The open-label, single-arm phase 1 trial enrolled 12 patients with advanced hepatocellular carcinoma who had progressed on or were intolerant to standard therapies. Patients received a single infusion of GPC3-targeted CAR T cells modified to express a dominant-negative TGFβ receptor II (dnTGFβRII). The primary endpoints were safety and feasibility; secondary endpoints included objective response rate and overall survival.
Efficacy and Safety Results
Among 12 evaluable patients, 4 achieved a partial response (33% objective response rate) and 6 had stable disease, yielding a disease control rate of 83%. Median progression-free survival was 7.2 months. No grade 3 or higher cytokine release syndrome or neurotoxicity occurred. The most common adverse events were grade 1-2 fever and fatigue.
Mechanism and Implications
The dnTGFβRII armoring is designed to counteract TGFβ-mediated immunosuppression in the tumor microenvironment. Preclinical models had shown that TGFβ signaling impairs CAR T cell function; this trial provides first-in-human evidence that blocking TGFβ signaling enhances CAR T cell persistence and antitumor activity in solid tumors.
What's Next
A phase 2 trial is being planned to confirm efficacy in a larger cohort. It remains unclear whether the approach will be effective in other solid tumor types or in combination with checkpoint inhibitors.
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CAR T cells show efficacy in advanced liver cancer trial
