title: Building on sipuleucel-T for immunologic treatment of castration-resistant prostate cancer.
abstract: BACKGROUND
  Sipuleucel-T is an autologous cellular immunotherapy approved by the US Food and Drug Administration for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. Its mechanism of action is based on stimulation of the patient's own immune system to target prostate cancer. Peripheral blood mononuclear cells, including antigen-presenting cells and T cells, are obtained from patients via leukapheresis and treated ex vivo with PA2024, a fusion protein consisting of prostatic acid phosphatase/granulocyte-macrophage colony-stimulating factor antigen.
  
  
  METHODS
  Data relating to the potential pharmacodynamic biomarkers associated with sipuleucel-T activity are reviewed, as well as considerations for patient selection and for sequencing sipuleucel-T with other prostate cancer treatments. Possible directions for future development are also discussed, including treatment of less advanced prostate cancer populations, combination treatment, and immune modulation.
  
  
  RESULTS
  Data from three randomized, double-blind, placebo-controlled phase III clinical trials of sipuleucel-T in patients with metastatic castration-rresistant prostate cancer have shown improvement in overall survival vs control. Here, we review its developing role in prostate cancer therapy and future directions for development.
  
  
  CONCLUSIONS
  There is potential to build on sipuleucel-T to further advance immunotherapy of prostate cancer.
authors.affiliation: Carolina Urologic Research Center/Atlantic Urology Clinics, Myrtle Beach, SC 29572, USA. nshore@gsuro.com
authors.forename: Neal D
authors.initials: ND
authors.lastname: Shore
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Mantz
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Dosoretz
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernandez
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Myslicki
authors.forename: Candice
authors.initials: C
authors.lastname: McCoy
authors.forename: Steven E
authors.initials: SE
authors.lastname: Finkelstein
authors.forename: Mayer N
authors.initials: MN
authors.lastname: Fishman
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D007167:Immunotherapy; D007937:Leukapheresis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D014020:Tissue Extracts / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D014020:Tissue Extracts; C511774:sipuleucel-T