title: Randomized, placebo-controlled, double-blinded chemoimmunotherapy clinical trial in a pet dog model of diffuse large B-cell lymphoma.
abstract: OBJECTIVE
  Active immunotherapy is a promising antitumoral strategy; however its use in combination with chemotherapy in dogs with large B-cell lymphoma (DLBCL) remains largely untested. Heat shock proteins (HSP) bind the small peptides they chaperone (HSPPC), allowing for immunization of the host against a large repertoire of tumor-associated antigens. Hydroxylapatite vehicles HSPPCs and acts as an immunologic adjuvant. The aim of this study was to show that an autologous vaccine with hydroxylapatite and tumor-derived HSPPCs is safe and therapeutically effective in dogs with DLBCL.
  
  
  METHODS
  Nineteen dogs with naturally occurring DLBCL were entered into a prospective randomized placebo-controlled double-blinded trial of HSPPCs-hydroxylapatite plus chemotherapy versus chemotherapy alone. Endpoints included time to progression (TTP), lymphoma-specific survival (LSS), and incidence of toxicoses.
  
  
  RESULTS
  Median first TTP after randomization to the vaccine arm was 304 days versus 41 days for the control arm (P = 0.0004). There was also a statistically significant difference in duration of second remission between the two groups (P = 0.02). Median LSS was 505 days for the vaccinated dogs versus 159 days for the unvaccinated dogs (P = 0.0018). Six vaccinated dogs achieved molecular remission, as shown by clonal immunoglobulin H (IgH) rearrangement. Toxicoses were comparable between the two treatment arms.
  
  
  CONCLUSIONS
  The results of this trial demonstrate that the autologous vaccine tested here is safe and efficacious in prolonging TTP and LSS in dogs with DLBCL when used in combination with dose-intense chemotherapy. On the basis of these results, additional evaluation of this novel therapeutic strategy is warranted in human DLBCL.
authors.affiliation: Authors' Affiliations: Centro Oncologico Veterinario, Sasso Marconi, Bologna; Department of Veterinary Sciences and Public Health, University of Milan; Department of Comparative Biomedicine and Food Science, University of Padova, Italy; Urodelia, St Lys, France; and Epidemiology advisor, London, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Marconato
authors.forename: Patrick
authors.initials: P
authors.lastname: Frayssinet
authors.forename: Nicole
authors.initials: N
authors.lastname: Rouquet
authors.forename: Stefano
authors.initials: S
authors.lastname: Comazzi
authors.forename: Vito Ferdinando
authors.initials: VF
authors.lastname: Leone
authors.forename: Paola
authors.initials: P
authors.lastname: Laganga
authors.forename: Federica
authors.initials: F
authors.lastname: Rossi
authors.forename: Massimo
authors.initials: M
authors.lastname: Vignoli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pezzoli
authors.forename: Luca
authors.initials: L
authors.lastname: Aresu
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use*; D004283:Dog Diseases / Q000628:therapy*; D004285:Dogs; D004311:Double-Blind Method; D017886:Durapatite / Q000276:immunology / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000276:immunology / Q000627:therapeutic use*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000628:therapy / Q000662:veterinary*
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D017886:Durapatite