Brief Summary:

Immunotherapy has become the major breakthrough and the most promising treatment, with the host of development of tumor biology, molecular biology and immunology. It has become the fourth tumor treatment model after traditional tumor therapies (surgery, chemotherapy, radiotherapy) . Mesothelin, PSCA, CEA, HER2, MUC1 and EGFRvIII are potential targets and spectacular paradigm in the diagnosis and treatment of pancreatic cancer. This study is for evaluation of the safety and efficacy of Mesothelin, PSCA, CEA, HER2, MUC1, EGFRvIII targeted and other CAR-T cell immunotherapy for pancreatic cancer.

Pancreatic Cancer

Drug: Chimeric antigen receptor T cell

Detailed Description:

Immunotherapy has become the major breakthrough and the most promising treatment, with the host of development of tumor biology, molecular biology and immunology. It has become the fourth tumor treatment model after traditional tumor therapies (surgery, chemotherapy, radiotherapy) . With the development of the research field, the CAR-T cell basis and clinical research of various targets have achieved good results. Mesothelin, PSCA, CEA, HER2, MUC1 and EGFRvIII are potential targets and spectacular paradigm in the diagnosis and treatment of pancreatic cancer. This study is for evaluation of the safety and efficacy of Mesothelin, PSCA, CEA, HER2, MUC1, EGFRvIII targeted and other CAR-T cell immunotherapy for pancreatic cancer.

Arms and Interventions

Arm

Experimental: CAR-T

A single dose of Chimeric antigen receptor T cells will be administered by vascular interventional mediated as one dose infusions. According to the patient's condition and weight, the intervention dose of aE7 CAR-T cells per kilogram of body weight was treated once.

Intervention

Drug: Chimeric antigen receptor T cell

Evaluate the efficacy and safety of targeted Mesothelin/PSCA/CEA/HER2/MUC1/, EGFRvIII and other chimeric antigen receptor engineered T cell immunotherapy in the treatment of pancreatic cancer.

Other Name: meso-CAR

Primary Outcome Measures  :

1. Number of patients with tumor response [ Time Frame: 8 weeks ]

Tumor response is assessmented with Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Secondary Outcome Measures  :

1. Number of patients with adverse event [ Time Frame: 8 weeks ]

Asverse event is evaluated with CTCAE, version 4.0

Criteria

Inclusion Criteria:

·       Imaging, pathology or biopsy confirmed as pancreatic cancer and it has metastasized, can not radical cured by surgery; patients restored good but there is still residual lesions, recurrence or metastasis 1 months after surgery;

·       Accepted more than 1 times chemotherapy which is invalid or unwilling to accept previous chemotherapy patients;

·       The corresponding antigens such as Meso and PSCA/ CEA/ HER2/ MUC1/ EGFRvIII were highly expressed;

·       Male patients aged between 18 and 65;

·       Life expectancy greater than 1 months;

·       Karnofsky score ≥ 60, ECOG≤ 2;

·       Important organ function as defined by the following: cardiac ejection fraction ≥ 50%; electrocardiogram showed no obvious abnormalities; creatinine clearance rate calculated by using Cockcroft- Gault formula ≥40ml/min ; ALT/AST≤ 3×the institution normal upper limit; total bilirubin ≤2.0mg/dl; coagulation function: PT/ APPT<2 ×the institution normal upper limit; SpO2 >92%; Blood: hemoglobin>80g/L, ANC ≥ 1, PLT ≥ 50×109/L;

·       There is measurable target lesion;

·       Voluntary informed consent is given.

Exclusion Criteria:

·       Immunosuppressive drugs or hormones were used a week before admission;

·       Severe active infection;

·       Human immunodeficiency virus (HIV) positive;

·       Active hepatitis B or C infection;

·       Past medical history of other malignancies. Not included: patients who have been cured at any time prior to the treatment of the skin basal or squamous cell carcinoma and cervical carcinoma in situ; the other tumor has not listed above, but has been used and only cured by surgery, without further treatment by other measures, the subjects of disease-free survival more than 5 years, can be included in the study;

·       Patients participating in other clinical trials;

·       The researchers thought the subjects were unfit for inclusion or unable to participate in or complete the study；

·       Patients with congenital immunodeficiency；

·       There is a history of myocardial infarction and serious arrhythmia within six months.