title: Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naïve prostate cancer.
abstract: OBJECTIVE
  To determine the toxicity, immunologic, and clinical activity of immunotherapy with irradiated, allogeneic, prostate cancer cells expressing granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with recurrent prostate cancer.
  
  
  METHODS
  A single-institution phase I/II trial was done in hormone therapy-naïve patients with prostate-specific antigen (PSA) relapse following radical prostatectomy and absence of radiologic metastases. Treatments were administered weekly via intradermal injections of 1.2 x 10(8) GM-CSF gene-transduced, irradiated, cancer cells (6 x 10(7) LNCaP cells and 6 x 10(7) PC-3 cells) for 8 weeks.
  
  
  RESULTS
  Twenty-one patients were enrolled and treated. Toxicities included local injection-site reactions, pruritus, and flu-like symptoms. One patient had a partial PSA response of 7-month duration. At 20 weeks post first treatment, 16 of 21 (76%) patients showed a statistically significant decrease in PSA velocity (slope) compared with prevaccination (P < 0.001). Injection site biopsies showed intradermal infiltrates consisting of CD1a+ dendritic cells and CD68+ macrophages, similar to previous clinical trials using autologous GM-CSF-transduced cancer cells. Posttreatment, patients developed new oligoclonal antibodies reactive against at least five identified antigens present in LNCaP or PC-3 cells. A high-titer antibody response against a 250-kDa antigen expressed on normal prostate epithelial cells was induced in a patient with partial PSA remission; titers of this antibody decreased when treatment ended, and subsequent PSA relapse occurred.
  
  
  CONCLUSIONS
  This non-patient-specific prostate cancer immunotherapy has a favorable safety profile and is immunologically active. Continued clinical investigation at higher doses and with longer boosting schedules is warranted.
authors.affiliation: Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA. jonathan.simons@emory.org
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Simons
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.forename: Bahar
authors.initials: B
authors.lastname: Mikhak
authors.forename: Michael
authors.initials: M
authors.lastname: Lim
authors.forename: Barbara
authors.initials: B
authors.lastname: Biedrzycki
authors.forename: Flavia
authors.initials: F
authors.lastname: Borellini
authors.forename: Shirley M
authors.initials: SM
authors.lastname: Clift
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Hege
authors.forename: Dale G
authors.initials: DG
authors.lastname: Ando
authors.forename: Steven
authors.initials: S
authors.lastname: Piantadosi
authors.forename: Richard
authors.initials: R
authors.lastname: Mulligan
authors.forename: William G
authors.initials: WG
authors.lastname: Nelson
mesh_terms: D000368:Aged; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology* / Q000601:surgery / Q000628:therapy*; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000601:surgery / Q000628:therapy*; D012008:Recurrence; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017430:Prostate-Specific Antigen