PD1 Integrated Anti-PSMA CART in Treating Patients With Castrate-Resistant Prostate Cancer

Inclusion Criteria:

* Fully understand and voluntarily sign informed consent.
* Aged 18 to 75 years old.
* Expected survival \> 6 months.
* CRPC patients:Serum testosterone reached castration level (\<50ng/dl or\<1.7nmol/L) and: prostate specific antigen (PSA) increased more than 50% at intervals of one week or three consecutive times, with PSA\>2 ng/ml; or imaging scans revealed two or more new lesions or enlargement of soft tissue lesions that met the criteria for evaluating solid tumor response.
* CRPC patients received abiraterone or chemotherapy for 3 months or more, and were ineffective or progressive (PSA continued to rise for 3 months, or bone scan/whole-body imaging showed local recurrence or new metastasis).
* Immunohistochemical staining of repetitive biopsy tissues showed the expression of PSMA in tumor cells was more than 50%.
* Eastern Cooperative Oncology Group (ECOG) score ≤2.
* Virological examination was negative.
* Hematological indexes: hemoglobin \> 100 g/L, platelet count \> 100×10\^9/L, absolute neutrophil count \> 1.5×10\^9/L.

Exclusion Criteria:

* Prior treatment with any CART therapy targeting any target.
* Prior treatment with any PSMA targeting therapy.
* Need steroid therapy, except physiological replacement therapy.
* Prior treatment with any immunotherapy, including tumor vaccine therapy, radium-223, checkpoint inhibitors and others.
* Subjects with severe mental disorders.
* Subjects with other malignant tumors.
* Subjects with severe cardiovascular diseases: a, New York Heart Association (NYHA) stage III or IV congestive heart failure; b, history of myocardial infarction or coronary artery bypass grafting (CABG) within 6 months; c, clinical significance of ventricular arrhythmia, or history of unexplained syncope, non-vasovagal or dehydration; d, history of severe non-ischemic cardiomyopathy; e, the left ventricular ejection fraction (left ventricular ejection fraction\< 55%) was decreased by echocardiography or multiple gated acquisition scan (within 8 weeks before peripheral blood mononuclear cell (PBMC) collection), and abnormal interventricular septal thickness and atrioventricular size associated with myocardial amyloidosis.
* Patients with ongoing or active infection.
* Organ function: a, Alanine aminotransferase or Aspartate aminotransferase \>2.5\*Upper limit of normal (ULN); Creatine kinase\>1.5\*ULN; Creatine kinase isoenzyme \>1.5\*ULN; Troponin T \>1.5\*ULN; b, Total bilirubin \>1.5\*ULN; c, Partial prothrombin time or activated partial thromboplastin time or international standardized ratio \> 1.5\*ULN without anticoagulant treatment.
* History of participation in other clinical studies within 3 months or treatment with any gene therapy product.
* Intolerant or allergic to cyclophosphamide or fludarabine.
* Subjects not appropriate to participate in this clinical study judged by investigators.