title: Intravesical Bacillus Calmette Guerin Combined with a Cancer Vaccine Increases Local T-Cell Responses in Non-muscle-Invasive Bladder Cancer Patients.
abstract: OBJECTIVE
  Treatments with cancer vaccines may be delivered as combination therapies for better efficacy. Addition of intravesical immunostimulation with bacteria promotes vaccine-specific T cells in the bladder and tumor-regression in murine bladder cancer models. Here, we determined whether an adjuvanted cancer vaccine can be safely administered with concomitant standard intravesical Bacillus-Calmette-Guérin (BCG) therapy and how vaccine-specific immune responses may be modulated in patients with non-muscle-invasive bladder cancer (NMIBC).
  
  
  METHODS
  In a nonrandomized phase I open-label exploratory study, 24 NMIBC patients, apportioned in three groups, received 5 injections of a subunit cancer vaccine (recMAGE-A3 protein+AS15) alone or in two combinations of intravesical BCG-instillations. Safety profiles were compared between the three treatment groups, considering single vaccine injections or BCG instillations and concomitant interventions. Immune responses in blood and urine were compared between treatment groups and upon BCG instillations.
  
  
  RESULTS
  The mild adverse events (AE) experienced by all the patients were similar to AE previously reported for this vaccine and standard BCG treatment. AEs were not increased by the double interventions, suggesting that BCG did not exacerbate the AE caused by the MAGE-A3 vaccine and vice-versa. All patients seroconverted after MAGE-A3 vaccination. In half of the patients, vaccine-specific T cells were induced in blood, irrespective of BCG treatment. Interestingly, such T cells were only detected in urine upon BCG-induced T-cell infiltration.
  
  
  CONCLUSIONS
  Cancer vaccines, including strong adjuvants, can be safely combined with intravesical BCG therapy. The increase of vaccine-specific T cells in the bladder upon BCG provides proof-of-principle evidence that cancer vaccines with local immunostimulation may be beneficial. Clin Cancer Res; 23(3); 717-25. ©2016 AACR.
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Laurent
authors: L
authors: Derré
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Valérie
authors: V
authors: Cesson
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Ilaria
authors: I
authors: Lucca
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Yannick
authors: Y
authors: Cerantola
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Massimo
authors: M
authors: Valerio
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Urs
authors: U
authors: Fritschi
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Yannis
authors: Y
authors: Vlamopoulos
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Rodolfo
authors: R
authors: Burruni
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Anne-Sophie
authors: AS
authors: Legris
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Florence
authors: F
authors: Dartiguenave
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Dalila
authors: D
authors: Gharbi
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Virginie
authors: V
authors: Martin
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Laurent
authors: L
authors: Vaucher
authors: Ludwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland.
authors: Daniel E
authors: DE
authors: Speiser
authors: Ludwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland.
authors: Pedro
authors: P
authors: Romero
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Patrice
authors: P
authors: Jichlinski
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. dnardell@hospvd.ch.
authors: Denise
authors: D
authors: Nardelli-Haefliger
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000283:Administration, Intravesical; D000951:Antigens, Neoplasm / Q000276:immunology*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D015653:Cystectomy / Q000379:methods; D016207:Cytokines / Q000652:urine; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007115:Immunization Schedule; D007167:Immunotherapy / Q000379:methods*; D007273:Injections, Intramuscular; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D010936:Plant Extracts / Q000008:administration & dosage; D031990:Quillaja; D011994:Recombinant Proteins / Q000276:immunology; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D001500:BCG Vaccine; D019496:Cancer Vaccines; D016207:Cytokines; D008050:Lipid A; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D010936:Plant Extracts; C483020:ProMune; D011994:Recombinant Proteins; C048436:monophosphoryl lipid A