title: A Phase I vaccine trial using dendritic cells pulsed with autologous oxidized lysate for recurrent ovarian cancer.
abstract: OBJECTIVE
  Ovarian cancer, like most solid tumors, is in dire need of effective therapies. The significance of this trial lies in its promise to spearhead the development of combination immunotherapy and to introduce novel approaches to therapeutic immunomodulation, which could enable otherwise ineffective vaccines to achieve clinical efficacy.
  
  
  BACKGROUND
  Tumor-infiltrating T cells have been associated with improved outcome in ovarian cancer, suggesting that activation of antitumor immunity will improve survival. However, molecularly defined vaccines have been generally disappointing. Cancer vaccines elicit a modest frequency of low-to-moderate avidity tumor-specific T-cells, but powerful tumor barriers dampen the engraftment, expansion and function of these effector T-cells in the tumor, thus preventing them from reaching their full therapeutic potential. Our work has identified two important barriers in the tumor microenvironment: the blood-tumor barrier, which prevents homing of effector T cells, and T regulatory cells, which inactivate effector T cells. We hypothesize that cancer vaccine therapy will benefit from combinations that attenuate these two barrier mechanisms.
  
  
  METHODS
  We propose a three-cohort sequential study to investigate a combinatorial approach of a new dendritic cell (DC) vaccine pulsed with autologous whole tumor oxidized lysate, in combination with antiangiogenesis therapy (bevacizumab) and metronomic cyclophosphamide, which impacts Treg cells.
  
  
  METHODS
  This study uses a novel autologous tumor vaccine developed with 4-day DCs pulsed with oxidized lysate to elicit antitumor response. Furthermore, the combination of bevacizumab with a whole tumor antigen vaccine has not been tested in the clinic. Finally the combination of bevacizumab and metronomic cyclophosphamide in immunotherapy is novel.
authors.affiliation: Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA, USA. lknd@mail.med.upenn.edu
authors.forename: Lana E
authors.initials: LE
authors.lastname: Kandalaft
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Chiang
authors.forename: Janos
authors.initials: J
authors.lastname: Tanyi
authors.forename: Greg
authors.initials: G
authors.lastname: Motz
authors.forename: Klara
authors.initials: K
authors.lastname: Balint
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mick
authors.forename: George
authors.initials: G
authors.lastname: Coukos
mesh_terms: D005260:Female; D006801:Humans; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D019496:Cancer Vaccines / Q000627:therapeutic use; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D003713:Dendritic Cells / Q000166:cytology; D005185:Fallopian Tube Neoplasms / Q000628:therapy; D007167:Immunotherapy / Q000379:methods; D010051:Ovarian Neoplasms / Q000628:therapy; D010534:Peritoneal Neoplasms / Q000628:therapy; D012008:Recurrence; D012107:Research Design; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D017321:Clinical Trials, Phase I as Topic
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D019496:Cancer Vaccines; D003520:Cyclophosphamide