Recently, a multicenter interventional trial conducted by a team led by Du Shunda, Director of the Department of Liver Surgery at PUMCH, in collaboration with multiple domestic and international institutions, was published in the leading gastroenterology and hepatology journal Gut (ranked among the top 5% by the Chinese Academy of Sciences, IF=25.8). This study explored hepatitis B surface antigen (HBsAg) as a target for T-cell therapy of hepatitis B virus (HBV)-induced late-stage hepatocellular carcinoma (HCC). This therapy demonstrated pronounced antiviral and antitumor activities and a safety profile manageable with supportive care, bringing hope for long-term survival to patients.
Globally, approximately 50% of HCC cases are associated with HBV infection. Despite continuous development of existing treatment methods, their efficacy remains limited, with median survival of advanced HCC patients in the Asia-Pacific region being less than 6 months. T-cell therapy is a cutting-edge treatment option for cancer, but the suitable target antigen for liver cancer remains unclear.
This study innovatively used HBsAg as the target. After HBV infects the human body, the viral DNA integrates into the host cell genome, causing infected liver cells to actively express HBsAg, which provides a precise "target" for T-cell therapy.
The study enrolled 6 patients with advanced hepatitis B-related HCC who had failed first-line, second-line, and third-line systemic antitumor treatments, using HBsAg-specific T-cell receptor (development code: SCG101) as monotherapy. Researchers isolated T cells from patients' bodies and processed them through specific techniques to amplify large quantities of T cells with enhanced antitumor activity that could specifically recognize HBsAg. These T cells were then reinfused into patients to precisely identify and attack three types of cells expressing HBsAg: HBV-infected liver cells, precancerous cells, and tumor cells.
The study found that within 2 weeks of SCG101 infusion, patients' median levels of serum HBsAg decreased by over 98%. The median follow-up period was 10.9 months; 3 patients died from disease progression, and the other 3 patients showed tumor shrinkage of 100%, 74.6%, and 19.5% respectively. One showed complete remission of the target lesion and remains progression-free for 27 months, still under ongoing follow-up; one other achieved a durable (>6 months) remission; one patient was lost to follow-up. Regarding safety, all patients experienced transient liver enzyme elevation, and 4 patients developed grade 3 cytokine release syndrome, but all recovered within 5 days. All adverse events could be effectively managed through standard treatment protocols. No neurotoxicity or dose-limiting toxicity was observed during the study period.
Previously, the liver surgery team at PUMCH had published related papers on SCG101's therapeutic mechanism, confirming the safety and feasibility of SCG101 application in preclinical models and the first patient. This study is the first to confirm the feasibility of this therapy at the clinical cohort level. The research found that this therapy not only directly inhibits tumor progression but can also reduce liver cancer recurrence risk by eliminating viral "reservoirs". The study suggests that dynamic changes in HBsAg levels, in vivo persistence of SCG101 cells, and tumor microenvironment characteristics may be important indicators for predicting responses to treatment.
Dr. Du Shunda stated that this research is currently still in the preliminary clinical research stage, warranting larger-scale, more systematic controlled trials to conduct more comprehensive risk-benefit analysis.
Du Shunda, Qu Xiujuan (Director of the Department of Medical Oncology at the First Hospital of China Medical University), and Professor Ulrike Protzer (Institute of Virology, Technical University of Munich, Germany) are co-corresponding authors of the article. Dr. Wu Xiang'an from PUMCH, Attending Physician Quan Dongmei from the Sixth People's Hospital of Shenyang, and Attending Physician Li Wei from Zhongshan Hospital Fudan University, Shanghai are co-first authors of the article.
Written by Wu Xiang’an and Gan Dingzhu