Clin Cancer Res: The results of the first phase of the car-T cell treatment of advanced hepatocellular carine in GPC3 were announced, with initial and significant results

Recently, the team of Professor Zibo, Director of the Oncology Intervention Department of Renji Hospital affiliated with Shanghai Jiaotong University School of Medicine, and Professor Li Zonghai of Koji Biomedical (Shanghai) Co., Ltd("Koji Bio" ),the world's first targeted CAR-T cell (CAR-GPC3) for the treatment of advanced hepatocellular carcinoma (HCC)published online in Clinical Cancerliver cancer is one of the major diseases that seriously threaten the life and health of our peopleEpidemiological survey data show that primary liver cancer is the fourth most common malignant tumor and the third leading cause of cancer death in China, with about 466,000 new cases each yearThe 5-year survival rate of early liver cancer was 50-60%, and the median survival of advanced liver cancer was 1 year, most patients are diagnosed in the middle and late stages and may lose the chance of surgeryAlthough interventional treatments such as local ablation and hepatic arterial embolism chemotherapy have brought new cure possibilities for patients with liver cancer who have lost their surgical opportunity, the recurrence and metastasis rate of patients with advanced liver cancer is high, and more efficient and low-toxic systemic treatment strains must be developedCAR-T cell therapy has become a new immunological therapy in recent yearsCAR-T Chinese named T lymphocytes modified by chimeric antigen receptors, and simply put it, T lymphocytes are immune active, like the army in the human body, and are the main force in killing tumor cellsCAR is a molecular modifier equipped with a navigation system capable of identifying tumor cells and other molecules involved in immune response, and other weapons, can be with T lymphocytes to accurately identify and destroy tumor cells expressing a certain gene, without harming normal human cells2015,led by Professor Zibo, Shanghai Keji Bio Company and Renji Hospital,, in the world to take the lead in theof GPC3-targeted CAR-T cell therapy of late HCC clinical trial , the treatment of 13 cases of GPC3 positive advanced HCC patients, the safety and effectiveness of treatment have obtained expected results After receiving the treatment, the patient's tolerance is good, safety is basically controlled, rare severe toxic side effects are rare, and the initial clinical benefits are shown in two prospective Phase 1 studies, adult patients with advanced GPC3 and HCC (Child-Pugh A) received autologous CAR-GPC3 T-cell therapy after cyclophosphamide and fluoradarabin-induced lymphatic removal The main purpose is to assess the safety of treatment As of July 24, 2019, 13 patients received CAR-GPC3 T cells with a median value of 19.9 x 10 8 The overall tolerance of the subjects was good, the main side effects were lymphocytes reduction, and 9 patients developed cytokine release syndrome (CRS), of which 8 were 1/2, with a good prognosis In 2 of the 13 patients, partial remission (PR) was 50.3%, 42.0% and 10.5% in 6 months, 1 year and 3 years, respectively, and the median survival time (OS) was 278 days (95% CI: 48,615 days) The survival time of these two patients was 20.5 and 44.2 months respectively, and one of the patients with stable disease had a lower cavity venous thrombosis, right atrial cancer and lymph node metastasis at the time of selection, and after treatment of AFP (a fetal protein) for a long period of time to maintain normal levels and long-term survival Such studies have shown the initial safety of CAR-GPC3 T-cell therapy We observed early signs of antitumor activity in CAR-GPC3 T cells in patients with advanced liver cancer , said that the study still has a lot to improve, the future is still a long way to go, but after all, CAR-T cells for the treatment of hepatocellular cancer and other solid tumors accumulated valuable experience, but also showed that CAR-T cells do have the potential to some liver cancer patients to bring long-term benefits GPC3 is a cancer embryo antigen that involves cell proliferation, differentiation, migration and apoptosis Expression is almost unseen in normal tissues, but expressed in 70-80% of HCC GPC3 is considered a highly promising target for tumor immunotherapy because of its tumor specificity Li Zonghai, "This is the world's first targeted car T cell clinical research, sincerely thank Professor Zibo team and all partners for their contribution and support, thank all patients and their families for their understanding and trust, without their courageous attempts, these original products are impossible to promote." I sincerely wish them to stay healthy, which is the greatest driving force for the development of new drugs At the same time, Cozie Bio will further conduct a series of exploratory studies on patients with gPC3 expression-positive liver cancer Kozy Bio will spare no effort to develop CAR-GPC3 T-cell products, with a view to the early benefit of the vast number of liver cancer patients "