CART-PSMA-TGFbetaRDN Cells in Treating Patients with Metastatic Castrate Resistant Prostate Cancer

Inclusion Criteria

• Metastatic castrate resistant prostate cancer
• >= 10% tumor cells expressing PSMA as demonstrated by immunohistochemistry analysis on fresh tissue
• Radiographic evidence of osseous metastatic disease and/or measurable, non-osseous metastatic disease (nodal or visceral)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
• Serum creatinine =< 1.5 mg/dl or creatinine clearance >= 60 cc/min
• Serum total bilirubin < 1.5 x upper limit of normal (ULN)
• Serum alanine aminotransferase (ALT)/aspartate aminotransferases (AST) < 2 x ULN
• Hemoglobin (Hgb) > 10 g/dl (within 4 weeks of study enrollment) * Subjects must not be transfusion dependent
• Platelet (PLT) > 100 k/ul (within 4 weeks of study enrollment) * Subjects must not be transfusion dependent
• Absolute neutrophil count (ANC) > 1.5 k/ul (within 4 weeks of study enrollment) * Subjects must not be transfusion dependent
• Evidence of progressive castrate resistant prostate adenocarcinoma, as defined by: * Castrate levels of testosterone (< 50 ng/ml) with or without the use of androgen-deprivation therapy AND * Evidence of one of the following measures of progressive disease in the 12 weeks preceding study enrollment: ** Soft tissue progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria ** Osseous disease progression with 2 or more new lesions on bone scan (as per Prostate Cancer Clinical Trials Working Group 2 [PCWG2 criteria]) ** Increase in serum PSA of at least 25% and an absolute increase of 2 ng/ml or more from nadir (as per PCWG2 criteria)
• Prior therapy with at least one standard 17alpha lyase inhibitor or second-generation anti-androgen therapy for the treatment of metastatic castrate resistant prostate cancer
• Provides written informed consent
• Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria

• Prior treatment with an immune-based therapy for the treatment of prostate cancer, including cancer vaccine therapies (such as sipuleucelT, PROSTVAC), immune checkpoint inhibitors, radium-223 and immunoconjugate therapies
• History of an active non-curative non-prostate primary malignancy within the prior 5 years
• Subjects with a rising PSA, but who have never had radiologic evidence of metastatic disease (i.e. ‘biochemical recurrence’)
• Subjects who require the chronic use of systemic corticosteroid therapy
• Subjects who have received > 3 prior therapies for the treatment of castrate resistant prostate cancer (excluding luteinizing hormone-releasing hormone agonists or antagonists, or first generation anti-androgen therapies). This includes subjects who received taxotere in noncastrate setting
• Subjects with class III/IV cardiovascular disability according to the New York Heart Association Classification
• Subjects with symptomatic vertebral metastases affecting spinal cord function (as determined by clinical history, physical exam, or magnetic resonance imaging [MRI] imaging)
• History of active autoimmune disease requiring immunosuppressive therapy
• Patients with ongoing or active infection
• History of allergy or hypersensitivity to study product excipients (human serum albumin, dimethyl sulfoxide [DMSO], and dextran 40)
• Active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection