Immunotherapy (APC8015, Provenge®) targeting prostatic acid phosphatase can induce durable remission of metastatic androgen-independent prostate cancer:: A phase 2 trial

BACKGROUND. Prostate cancer is the most commonly diagnosed malignancy in American men, yet treatment of its metastatic androgen-independent form remains inadequate. This mandates development of new therapies such as immunotherapy. In this Phase 2 trial, we determined the efficacy of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein containing prostatic acid phosphatase (PAP) and GM-CSF. METHODS. We enrolled 21 patients with histologically documented androgen-independent prostate carcinoma that could be evaluated by radionuclide bone scan or computed tomography scan. APC8015 was prepared from a leukapheresis product; it contained autologous CD54-positive PA2024-loaded APCs with admixtures of monocytes, macrophages, B and T cells. APC8015 was infused intravenously twice, 2 weeks apart. Two weeks after the second infusion, patients received three subcutaneous injections of 1.0 mg of PA2024 1 month apart. We monitored patients' physical condition, immune response, and laboratory parameters. RESULTS. Nineteen patients could be evaluated for response to treatment. The median time to progression was 118 days. Treatment was tolerated reasonably well; most adverse effects were secondary to APC8015 and were NCI Common Toxicity Criteria Grade 1-2. Four of the 21 patients reported Grade 3-4 adverse events. Two patients exhibited a transient 25-50% decrease in prostate-specific antigen (PSA). For a third patient, PSA dropped from 221 ng/ml at baseline to undetectable levels by week 24 and has remained so for more than 4 years. In addition, this patient's metastatic retroperitoneal and pelvic adenopathy has resolved. PBMC collected from patients for at least 16 weeks proliferated upon in vitro stimulation by PA2024. For the patient with responsive disease, PBMC could be stimulated for 96 weeks. CONCLUSIONS. This study demonstrates a definite clinical response of androgen-independent prostate cancer to APC immunotherapy. Currently we are studying this mode of therapy in Phase 3 trials. (C) 2004 Wiley-Liss, Inc.