晚期肝细胞癌对磷脂酰肌醇蛋白聚糖 3 特异性 CAR-T 细胞联合索拉非尼的长期完全缓解：一例病例报告

The clinical efficacy of current therapies for Hepatocellular carcinoma (HCC) are unsatisfactory. In recent years, chimeric antigen receptor (CAR) T-cell therapies have been developed for solid tumors including advanced HCC (aHCC), but limited progress has been made.

Glypican-3 is a promising immunotherapeutic target for HCC since it is specifically highly expressed in HCC. A previous study indicated that GPC3-targeted CAR T-(CAR-GPC3) cells were well-tolerated and had prolonged survival for HCC patients and that Sorafenib could increase the antitumor activities of CAR-GPC3 T-cells against HCC in mouse models.

Here, we report a patient with aHCC who achieved a complete response (CR) and a long survival period after the combination therapy of CAR-GPC3 T-cell plus sorafenib. A 60-year-old Asian male diagnosed with hepatitis B virus (HBV) related HCC developed liver recurrence and lung metastasis after liver tumor resection and trans-arterial chemoembolization therapy. The patient also previously received microwave ablation therapy for lung metastasis. After the enrollment, the patient underwent leukapheresis for CAR-GPC3 T-cells manufacturing. Seven days after leukapheresis, the patient started to receive 400 mg of Sorafenib twice daily. The patient received 4 cycles of CAR-GPC3 T cells (CT011) treatment and each cycle was divided into two infusions.

Prior to each cycle of CT011 treatment, lymphodepletion was performed. The lymphodepletion regimen was cyclophosphamide 500 mg/m 2 /day for 2 to 3 days, and fludarabine 20-25 mg/m 2 /day for 3 to 4 days. A total of 4 10 9 CAR-GPC3 T cells were infused. The CT011 plus Sorafenib combination therapy was well tolerated.

All the grade 3 AEs were hematological toxicities which were deemed an expected event caused by the preconditioning regimen. This patient obtained partial responses from the 3 rd month and achieved CR in the 12 th month after the first cycle of CT011 infusion according to the RECIST1. 1 assessment. The tumor had no progression for more than 36 months and maintained the CR status for more than 24 months after the first infusion.