Clinical Study of Safety and Efficacy of Enhanced PSMA CAR- T in Refractory CRPC

Inclusion Criteria: 1. Fully understood and voluntarily signed informed consent for this study; 2. male, aged 18-75 years; 3. expected survival of more than 6 months; 4. metastatic castration-resistant prostate adenocarcinoma (CRPC) patients. 5. Receiving CRPC standard treatment (such as new endocrine therapy, chemotherapy and radium-223, etc., one or more of the combination therapy) after the diagnosis of CRPC, ineffective or progressive disease (PSA continued to rise for 3 months, or bone scan/whole-body MRI/PET-CT showed local recurrence or new metastatic lesions, demonstrating disease progression); 6. PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment; 7. ECOG score \< 2 ; 8. virological examination HAV (hepatitis A virus), HBV (hepatitis B virus), HCV (hepatitis C virus), HIV (human immunodeficiency virus), TP (Treponema pallidum) quantitative detection was negative, (antigen and antibody screening method unknown, confirmed by nucleic acid method); hematological parameters met the following criteria: a. hemoglobin \> 100 g/L; b. platelet count \> 100 × 109/L; c. neutrophils \> 1.5 × 109/L. Exclusion Criteria: Subjects meeting any of the following exclusion criteria will be excluded: 1. have received any previous treatment with CAR-T therapy ; 2. have received any previous treatment that targets PSMA; 3. tumor pathology suggests a special type of prostate cancer (e.g., neuroendocrine prostate cancer, etc.) 4. severe mental disorders; 5. suffered from previous malignancies, except for the following: a. basal cell carcinoma or squamous cell carcinoma after standardized treatment; b. having a primary malignancy, but completely resected, with a complete remission time of ≥ 5 years. 6. Subjects with severe cardiovascular disease; a.New York Heart Association (NYHA) stage III or IV congestive heart failure; b.Myocardial infarction ≤ 6 months prior to enrollment or coronary artery bypass graft (CABG); c.Clinically significant ventricular arrhythmia, or history of unexplained syncope, nonvasovagal or not due to dehydration; d.History of severe non-ischemic cardiomyopathy; e.Decreased left ventricular ejection fraction (LVEF \< 55%) as assessed by echocardiogram or multigated acquisition (MUGA) scan, abnormal interventricular septal thickness and atrioventricular size associated with myocardial amyloidosis; 7. active infectious disease or any major infectious event requiring high grade antibiotics; 8. organ function in the following abnormalities: a. serum aspartate aminotransferase or alanine aminotransferase \> 2.5ULN; CK \> ULN; CK-MB \> ULN; TnT \> 1.5ULN; b. total bilirubin \> 1.5ULN; c. partial prothrombin time or activated partial thromboplastin time or international normalized ratio \> 1.5ULN in the absence of anticoagulant therapy; 9. participation in other clinical studies in the past three months or previous treatment with any gene therapy product; 10. intolerance or hypersensitivity to cyclophosphamide and fludarabine chemotherapy; 11. unsuitability to participate in this clinical study in the opinion of the investigator.