A Clinical Research of CAR T Cells Targeting EpCAM Positive Cancer (CARTEPC)

Brief Summary:

The purpose of this study is to evaluate the safety and efficacy of EpCAM-specific CAR T Cells infusion for EpCAM positive Cancer.

*Colon Cancer *Esophageal *Carcinoma *Pancreatic Cancer *Prostate Cancer *Gastric Cancer *Hepatic Carcinoma

Biological: CAR-T cell immunotherapy

Detailed Description:

This study is being conducted to evaluate the safety and efficacy of Chimeric antigen receptor (CAR) T cells targeting EpCAM in treating patients with EpCAM positive cancer. In the research, the investigators design a novel CAR consists of a EpCAM targeting antibody scFv with two intracellular signaling domains derived from CD3 zeta and CD28. Autologous T cells will be gene-engineered with the CAR gene using a lentivirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. The infusion dose is (1-10)×106 EpCAM-CAR positive T cells/kg, and the specific cells numbers depends on the situation of individual CAR-T cells preparation. The way of infusion is vascular interventional mediated or endoscopy, and the cells perfusion process would lasts 15min to 30min, and the specific time depends on patent's tumor-burdened state. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.

Arms and Interventions

Arm

Experimental: CAR-T cell immunotherapy

Enrolled patients will receive CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at EpCAM antigen by infusion.

Interventions

Biological: CAR-T cell immunotherapy

This CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at EpCAM antigen.

Primary Outcome Measures :

1.     Toxicity profile of the EpCAM targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0 [ Time Frame: up to 24 months ]

Observe and handle the toxicity profile of the EpCAM targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0

Secondary Outcome Measures :

1.     Survival time of anti-EpCAM CAR T cells in vivo [ Time Frame: up to 24 months ]

Detect the existence of CAR-T cells in the blood of participants through flow cytometry

2.     Anti-tumor efficacy of CAR-T therapy by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 [ Time Frame: up to 24 months ]

Anti-tumor efficacy of CAR-T therapy for patients with EpCAM positive cancers was assessed by RECIST v1.1

Criteria

Inclusion Criteria:

1.     Relapsed or refractory EpCAM positive cancer.

2.     KPS > 60.

3.     Life expectancy>3 months.

4.     Gender unlimited, age from 18 years to 80 years.

5.     Assessable lesions with a minimum size of 10mm by CT scan or MRI.

6.     Acceptable organ function Hematology:

• Absolute neutrophil count greater than 800/mm^3 without the support of filgrastim.

• White blood cell (WBC) (> 2000/mm^3).

• Platelet count greater than 50,000/mm^3.

• Hemoglobin greater than 9.0 g/dl.

7.     No other serious diseases(autoimmune disease, immunodeficiency etc.).

8.     Adequate cardiac function (LVEF ≥ 40%).

9.     No other tumors.

10. Patients volunteer to participate in the research.

Exclusion Criteria:

1.     Allergic to cytokines.

2.     Uncontrolled active infection.

3.     Acute or chronic GVHD.

4.     MODS.

5.     Treated with T cell inhibitor.

6.     HIV affected.

7.     Pregnancy