pd1 integrated anti-psma cart in treating patients with castrate-resistant prostate cancer

Conditions: Castrate-Resistant Prostate Cancer

Summary: pd1-psma-cart in treating patients with castrate-resistant prostate cancer

clinical trial for the safety and efficacy of non-viral programmed cell death protein-1(pd1) integrated anti-prostate-specific-membrane-antigen(psma) chimeric antigen receptor t(cart) cells in the treatment of refractory castrate-resistant prostate cancer(crpc)

Eligibility criteria:
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 (\ 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.

Keywords: castrate-resistant prostate cancer