title: Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings.
abstract: OBJECTIVE
  To determine the immunogenicity and antitumor activity of a vaccine consisting of autologous, tumor-derived heat shock protein gp96-peptide complexes (HSPPC-96, Oncophage; Antigenics, Inc, Woburn, MA) in metastatic (American Joint Committee on Cancer stage IV) melanoma patients.
  
  
  METHODS
  Sixty-four patients had surgical resection of metastatic tissue required for vaccine production, 42 patients were able to receive the vaccine, and 39 were assessable after one cycle of vaccination (four weekly injections). In 21 patients, a second cycle (four biweekly injections) was given because no progression occurred. Antigen-specific antimelanoma T-cell response was assessed by enzyme-linked immunospot (ELISPOT) assay on peripheral blood mononuclear cells (PBMCs) obtained before and after vaccination. Immunohistochemical analyses of tumor tissues were also performed.
  
  
  RESULTS
  No treatment-related toxicity was observed. Of 28 patients with measurable disease, two had a complete response (CR) and three had stable disease (SD) at the end of follow-up. Duration of CR was 559+ and 703+ days, whereas SD lasted for 153, 191, and 272 days, respectively. ELISPOT assay with PBMCs of 23 subjects showed a significantly increased number of postvaccination melanoma-specific T-cell spots in 11 patients, with clinical responders displaying a high frequency of increased T-cell activity. Immunohistochemical staining of melanoma tissues from which vaccine was produced revealed high expression of both HLA class I and melanoma antigens in seven of eight clinical responders (two with CR, three with SD, and the three with long-term disease-free survival) and in four of 12 nonresponders.
  
  
  CONCLUSIONS
  Vaccination of metastatic melanoma patients with autologous HSPPC-96 is feasible and devoid of significant toxicity. This vaccine induced clinical and tumor-specific T-cell responses in a significant minority of patients.
authors.affiliation: Unit of General Surgery 2, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Filiberto
authors.initials: F
authors.lastname: Belli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.forename: Licia
authors.initials: L
authors.lastname: Rivoltini
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.forename: Giovanna
authors.initials: G
authors.lastname: Andreola
authors.forename: Mario Roberto
authors.initials: MR
authors.lastname: Sertoli
authors.forename: Gianfrancesco
authors.initials: G
authors.lastname: Gallino
authors.forename: Adriano
authors.initials: A
authors.lastname: Piris
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cattelan
authors.forename: Ivano
authors.initials: I
authors.lastname: Lazzari
authors.forename: Matteo
authors.initials: M
authors.lastname: Carrabba
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scita
authors.forename: Cristina
authors.initials: C
authors.lastname: Santantonio
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pilla
authors.forename: Gabrina
authors.initials: G
authors.lastname: Tragni
authors.forename: Claudia
authors.initials: C
authors.lastname: Lombardo
authors.forename: Flavio
authors.initials: F
authors.lastname: Arienti
authors.forename: Alfonso
authors.initials: A
authors.lastname: Marchianò
authors.forename: Paola
authors.initials: P
authors.lastname: Queirolo
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
authors.forename: Agata
authors.initials: A
authors.lastname: Cova
authors.forename: Elda
authors.initials: E
authors.lastname: Lamaj
authors.forename: Lucio
authors.initials: L
authors.lastname: Ascani
authors.forename: Roberto
authors.initials: R
authors.lastname: Camerini
authors.forename: Marco
authors.initials: M
authors.lastname: Corsi
authors.forename: Natale
authors.initials: N
authors.lastname: Cascinelli
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Lewis
authors.forename: Pramod
authors.initials: P
authors.lastname: Srivastava
authors.forename: Giorgio
authors.initials: G
authors.lastname: Parmiani
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007150:Immunohistochemistry; D007167:Immunotherapy; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012074:Remission Induction; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006680:HLA Antigens; D006360:Heat-Shock Proteins