Combined local therapy and CAR‐GPC3 T‐cell therapy in advanced hepatocellular carcinoma: a proof‐of‐concept treatment strategy

作者：Yao Shi, Donghua Shi, Jiachang Chi, Dan Cui, Xiaoyin Tang, Yan Lin, Siying Wang, Zonghai Li, Haojie Jin, Bo Zhai · 发表于：癌症：英文版 · 年份：2023 · DOI：10.1002/cac2.12472 · 被引用次数：32 · 研究领域：CAR-T cell therapy research、Nanowire Synthesis and Applications、Cancer Immunotherapy and Biomarkers

Available evidence regarding the most suitable treatment strategies for hepatocellular carcinoma (HCC) with inferior vena cava tumor thrombus (IVCTT) is extremely limited, and the median overall survival time for these patients after liver resection is only 17.76 months [1]. Other local or systemic treatments for HCC with IVCTT result in a median overall survival time ranging from 5.88 to 15.36 months [1-3]. Thus, new therapeutic strategies are urgently needed to improve the survival of HCC patients with IVCTT. Chimeric antigen receptor (CAR) T-cell therapy has seen success in treating B-cell neoplasms with impressive outcomes [4]. However, this therapy alone has shown limited efficacy on solid tumors, such as HCC [5]. In this study, we put forward a proof-of-concept treatment strategy that local therapy plus CAR-glypican-3 (CAR-GPC3) T-cell therapy might be effective for advanced HCC patients and reported the application of this combination in two GPC3-positive HCC patients with rapidly progressing IVCTT. The study protocol can be found in the Supplementary Materials. In brief, both patients received local therapy to treat liver lesions and IVCTT, followed by sequential infusions of CAR-GPC3 T-cells, and achieved more than 5-year disease-free survival and more than 8-year overall survival. For case 1, a 50-year-old male patient (Patient A) with hepatitis B cirrhosis was diagnosed with Ib-stage HCC according to China Liver Cancer Staging (CNLC) in December 2014. The patient's...