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면역치료 | 위암 CAR-T 임상 EpCAM-specific

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작성자 HK HIS 작성일19-09-16 18:18 조회4,101회 댓글0건

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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.

 

 

Intervention

 

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

  1. 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

 

 

 

Ages Eligible for Study:  

18 Years to 80 Years   (Adult, Older Adult)

Sexes Eligible for Study:  

All

Accepts Healthy Volunteers:  

No

 

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:

 

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

 

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

 

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

 

o   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.

 

 

 

 

 

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