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

Prior treatment

• have received any previous treatment with CAR-T therapy ;
• have received any previous treatment that targets PSMA;
• participation in other clinical studies in the past three months or previous treatment with any gene therapy product;

Other illness

• tumor pathology suggests a special type of prostate cancer (e.g., neuroendocrine prostate cancer, etc.)
• severe mental disorders;
• active infectious disease or any major infectious event requiring high grade antibiotics;
• intolerance or hypersensitivity to cyclophosphamide and fludarabine chemotherapy;

Lab values

• 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;
• 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;

Age

• 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.

Other

• Subjects meeting any of the following exclusion criteria will be excluded:
• unsuitability to participate in this clinical study in the opinion of the investigator.

• Fully understood and voluntarily signed informed consent for this study;
• male, aged 18-75 years;
• expected survival of more than 6 months;
• metastatic castration-resistant prostate adenocarcinoma (CRPC) patients.
• 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);
• PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment;
• ECOG score \< 2 ;
• 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.