light-psma-cart in treating patients with castrate-resistant prostate cancer

Conditions: Castrate-Resistant Prostate Cancer

Summary: this is a single center, single arm phase i study to establish the safety and efficacy of intravenously administered lentivirally transduced light-psma-specific car modified autologous t cells (psma-cart cells) in patients with crpc.

this is a phase i study evaluating the safety and efficacy of psma targeting autologous car t cells co-expressing light in a 3+3 dose escalation design. cohort 1 subjects (n=3 or 6) will receive a tolal dose of 3x 10\^6/kg body weight (kgbw) light-psma-cart cells at split doses after a conditioning chemotherapeutic regimen(cy+flu). if 1 dlt/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level. if 0 dlt/3 subjects or 1 dlt/6 subjects occurs, the study will advance to cohort 2, with a total dose of 6 x 10\^6/ kgbw.

Eligibility criteria:
inclusion criteria: * fully understand and voluntarily sign informed consent. * male, aged 18 to 75 years old. * expected survival \> 6 months. * crpc patients: prostate cancer is still progressing after continuous androgen deprivation therapy. including, castrate levels of serum testosterone (\ 1 ug/l; 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 mri/pet-ct showed local recurrence or new metastasis). * immunohistochemical staining of repetitive biopsy tissues showed the expression of psma in tumor cells was more than 50%. * ecog score \<2. * hgb \> 10 g/dl. * plt \> 100×109/l. * anc \> 1.5×109/l. exclusion criteria: subjects who meet any of the following exclusion criteria will be excluded * prior treatment with any immunotherapy, including cart therapy, tumor vaccine therapy, radium-223, checkpoint inhibitors. * prior treatment with any psma targeting therapy. * subjects with severe mental disorders. * 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 (lvef \< 55%) was decreased by echocardiography or muga scan (within 8 weeks before pbmc collection), and abnormal interventricular septal thickness and atrioventricular size associated with myocardial amyloidosis. * patients with ongoing or active infection. * aspartate aminotransferase or alanine aminotransferase \>2.5\*uln; ck\>1.5\*uln; ck-mb\>1.5\*uln; tnt\>1.5\*uln. * total bilirubin \>1.5\*uln. * 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