title: A dendritic cell vaccine pulsed with autologous hypochlorous acid-oxidized ovarian cancer lysate primes effective broad antitumor immunity: from bench to bedside.
abstract: OBJECTIVE
  Whole tumor lysates are promising antigen sources for dendritic cell (DC) therapy as they contain many relevant immunogenic epitopes to help prevent tumor escape. Two common methods of tumor lysate preparations are freeze-thaw processing and UVB irradiation to induce necrosis and apoptosis, respectively. Hypochlorous acid (HOCl) oxidation is a new method for inducing primary necrosis and enhancing the immunogenicity of tumor cells.
  
  
  METHODS
  We compared the ability of DCs to engulf three different tumor lysate preparations, produce T-helper 1 (TH1)-priming cytokines and chemokines, stimulate mixed leukocyte reactions (MLR), and finally elicit T-cell responses capable of controlling tumor growth in vivo.
  
  
  RESULTS
  We showed that DCs engulfed HOCl-oxidized lysate most efficiently stimulated robust MLRs, and elicited strong tumor-specific IFN-γ secretions in autologous T cells. These DCs produced the highest levels of TH1-priming cytokines and chemokines, including interleukin (IL)-12. Mice vaccinated with HOCl-oxidized ID8-ova lysate-pulsed DCs developed T-cell responses that effectively controlled tumor growth. Safety, immunogenicity of autologous DCs pulsed with HOCl-oxidized autologous tumor lysate (OCDC vaccine), clinical efficacy, and progression-free survival (PFS) were evaluated in a pilot study of five subjects with recurrent ovarian cancer. OCDC vaccination produced few grade 1 toxicities and elicited potent T-cell responses against known ovarian tumor antigens. Circulating regulatory T cells and serum IL-10 were also reduced. Two subjects experienced durable PFS of 24 months or more after OCDC.
  
  
  CONCLUSIONS
  This is the first study showing the potential efficacy of a DC vaccine pulsed with HOCl-oxidized tumor lysate, a novel approach in preparing DC vaccine that is potentially applicable to many cancers.
authors.affiliation: Ovarian Cancer Research Center, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. chchiang@mail.med.upenn.edu
authors.forename: Cheryl Lai-Lai
authors.initials: CL
authors.lastname: Chiang
authors.forename: Lana E
authors.initials: LE
authors.lastname: Kandalaft
authors.forename: Janos
authors.initials: J
authors.lastname: Tanyi
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Hagemann
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Motz
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Svoronos
authors.forename: Kathleen
authors.initials: K
authors.lastname: Montone
authors.forename: Gina M
authors.initials: GM
authors.lastname: Mantia-Smaldone
authors.forename: Lori
authors.initials: L
authors.lastname: Smith
authors.forename: Harvey L
authors.initials: HL
authors.lastname: Nisenbaum
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Levine
authors.forename: Michael
authors.initials: M
authors.lastname: Kalos
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Czerniecki
authors.forename: Drew A
authors.initials: DA
authors.lastname: Torigian
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Powell
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mick
authors.forename: George
authors.initials: G
authors.lastname: Coukos
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology; D007167:Immunotherapy; D016753:Interleukin-10 / Q000097:blood; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D010084:Oxidation-Reduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000941:Antigens; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016753:Interleukin-10; D006997:Hypochlorous Acid