CD276-targeted Chimeric Antigen Receptor T Cells in Treatment With Advanced Pancreatic Cancer

1. Age 18-75 years old (≥18 years old, ≤75 years old), no gender limit;
2. The subject voluntarily participates in the study, and he or his legal guardian signs the "Informed Consent";
3. Unresectable, locally advanced recurrence or metastatic pancreatic cancer diagnosed by histopathological examination; according to the American Joint Committee on Cancer (AJCC) TNM staging system (2017 version 8), diagnosed as stage III or IV pancreatic cancer ；
4. According to the RECIST 1.1 standard, there are clear measurable and evaluable lesions;
5. The tumor tissue was confirmed by immunohistochemical staining, and CD276 expression was positive;
6. The subject must have received first-line treatment;
7. The subject must be unsuitable for radical treatment, such as radical chemotherapy and/or surgery/immune checkpoint inhibitors, or refuse surgical resection
8. Within 2 weeks before cell therapy, have not received antibody drug treatment;
9. The ECOG score is 0-2 points;
10. The subject has no contraindications for peripheral blood apheresis;
11. The expected survival time is more than 3 months

Exclusion Criteria:

1. Those who have a history of allergies to any of the ingredients in cell products;
2. Routine blood examinations have the following conditions: WBC≦1×109/L, absolute centrioles ANC≦0.5×109/L, absolute lymphocyte value ALC≦0.5×109/L, PLT≦25×109/L;
3. The following conditions in laboratory tests include, but are not limited to, serum total bilirubin ≥ 1.5 mg/dl; serum ALT or AST greater than 2.5 times the upper limit of normal; blood creatinine ≥ 2.0 mg/dl;
4. According to the New York Heart Association (NYHA) cardiac function classification standards, patients with grade III or IV cardiac insufficiency; or echocardiographic examination of left ventricular ejection fraction (LVEF) \<50%;
5. Abnormal lung function, blood oxygen saturation in indoor air \<92%;
6. Myocardial infarction, cardiovascular angioplasty or stenting, unstable angina pectoris, or other serious clinical heart diseases within 12 months before enrollment;
7. High blood pressure level 3 and poor blood pressure control with medication;
8. Previously suffering from head injury, disturbance of consciousness, epilepsy, more serious cerebral ischemia or cerebral hemorrhage disease;
9. Patients with autoimmune diseases, immunodeficiencies, or other patients who need immunosuppressive therapy;
10. There is an uncontrolled active infection;
11. Have used any CAR-T cell products or other genetically modified T cell therapies before;
12. Live vaccination within 4 weeks before enrollment;
13. HIV, HBV, HCV and TPPA/RPR infected persons, and HBV carriers;
14. The subject has a history of alcoholism, drug abuse or mental illness;
15. The subject has participated in any other clinical research within 3 months before joining this clinical research;
16. Female subjects who have any of the following conditions: a) are pregnant/lactating; or b) have a pregnancy plan during the trial period; or c) have fertility and cannot take effective contraceptive measures;
17. The researcher believes that the subject has other conditions that are not suitable for participating in this research