title: Harnessing naturally occurring tumor immunity: a clinical vaccine trial in prostate cancer.
abstract: BACKGROUND
  Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC) vaccine.
  
  
  RESULTS
  We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling time (p = 0.003) were identified when we compared data before and after vaccination.
  
  
  CONCLUSIONS
  An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00289341.
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Rockefeller University, New York, New York, United States of America.
authors.forename: Mayu O
authors.initials: MO
authors.lastname: Frank
authors.forename: Julia
authors.initials: J
authors.lastname: Kaufman
authors.forename: Suyan
authors.initials: S
authors.lastname: Tian
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: Salina
authors.initials: S
authors.lastname: Parveen
authors.forename: Nathalie E
authors.initials: NE
authors.lastname: Blachère
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
authors.forename: Susan
authors.initials: S
authors.lastname: Slovin
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
authors.forename: Robert B
authors.initials: RB
authors.lastname: Darnell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D064987:Cell- and Tissue-Based Therapy; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000276:immunology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D017430:Prostate-Specific Antigen
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