NCT03198546招募中1 期
CAR-T Cell Targeting GPC3 for Immunotherapy of Hepatocellular Carcinoma: Phase I Clinical Trial
Second Affiliated Hospital of Guangzhou Medical University2 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2017年7月1日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Number of Patients with Dose Limiting Toxicity
研究概览
简要总结
The third/fourth generation of CAR-T cells that target GPC3 (GPC3-CART cell) and/or soluble TGFβ (GPC3/TGFβ-CART )have been constructed and their anti-HCC function has been verified by multiple in vitro and in vivo studies. Clinical studies will be performed to test the anti-cancer function by the GPC3/TGFβ-CAR-T cells in human HCC patients with GPC3 expression. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/TGFβ-CAR-T cell immunotherapy on human will firstly be tested.
详细描述
- Choose appropriate patients with advanced hepatocellular carcinoma,with written consent for this study;
- Perform biopsy to determine the expression of GPC3 of the tumor by western blotting or IHC;
- Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with GPC3/TGFβ targeting CAR (or/and scfv/cytokines-secreting), amplify the number of transfected T cells as needed, test the quality and killing activity of the GPC3/TGFβ-CART cells and then transplant back the patients via systemic or local infusions (via artery or intra-tumor), and follow up closely to collect related results as needed;
- To enhance the killing capability, CD4+ T cells are genetically engineered to express TGFβ-CAR and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Tigit; CD8+T cells are constructed to express GPC3-DAP10-CAR with knockdown of PD1/HPK1;
- Evaluate the clinical results as needed.
- Will also perform the similar clinical trial on lung squamous carcinoma with the GPC3 expression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients with advanced HCC,which express GPC3 protein.
- •Life expectancy >12 weeks
- •Child-Pugh-Turcotte score <7
- •Adequate heart,lung,liver,kidney function
- •Available autologous transduced T cells with greater than or equal to 20% expression of GPC3 CAR determined by flow-cytometry and killing of GPC3-positive targets greater than or equal to 20% in cytotoxicity assay
- •Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -
排除标准
- •Had accepted gene therapy before;
- •Tumor size more than 25cm;
- •Severe virus infection such as HBV,HCV,HIV,et al
- •Known HIV positivity
- •History of liver transplantation
- •Active infectious disease related to bacteria, virus,fungi,et al
- •Other severe diseases that the investigators consider not appropriate;
- •Pregnant or lactating women
- •Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
- •Other conditions that the investigators consider not appropriate. -
结局指标
主要结局
Number of Patients with Dose Limiting Toxicity
时间窗: three months
A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GPC3-T2-CAR T cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.
次要结局
- Percent of Patients with best response as either complete remission or partial remission.(three months)
- Median CAR-T cell persistence(Five years)
研究者
研究点 (2)
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