Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells

Purpose: Provenge (Dendreon Corp, Seattle, WA) is an immunotherapy product consisting of autologous dendritic cells loaded ex vivo with a recombinant fusion protein consisting of prostatic acid phosphatase (PAP) linked to gra nulocyte-macrophage colony-stimulating factor. Sequential phase I and phase II trials were performed to determine the safety and efficacy of Provenge and to assess its capacity to break immune Proverance to the normal tissue antigen PAP. Patients and Methods: All patients had hormone-refractory prostate cancer. Dendritic-cell precursors were harvested by leukapheresis in weeks 0, 4, 8, and 24, loaded ex vivo with antigen for 2 days, and then infused intraveno usly over 30 minutes. Phase I patients received increasing doses of Proveng e, and phase II patients received all the Provenge that could be prepared f rom a leukapheresis product, Results: Patients tolerated treatment well. Fever, the most common adverse event, occurred after 15 infusions (14.7%). All patients developed immune r esponses to the recombinant fusion protein used to prepare Provenge, and 38 % developed immune responses to PAP, Three patients had a more than 50% dec line in prostate-specific antigen (PSA) level, and another three patients h ad 25% to 49% decreases in PSA, The time to disease progression correlated with development of an immune response to PAP and with the dose of dendriti c cells received. Conclusion: Provenge is a novel immunotherapy agent that is safe and breaks tolerance to the tissue antigen PAP. Preliminary evidence for clinical eff icacy warrants further exploration. (C) 2000 by American Society of Clinica l Oncology.