title: A phase II trial of vaccination with autologous, tumor-derived heat-shock protein peptide complexes Gp96, in combination with GM-CSF and interferon-alpha in metastatic melanoma patients.
abstract: The aim of this study was to determine the immunogenicity and antitumor activity of autologous, tumor-derived heat shock protein gp96-peptide complex vaccine (HSPPC-96; Oncophage given with GM-CSF and IFN-alpha in pre-treated metastatic (AJCC stage IV) melanoma patients. Patients underwent surgical resection of metastatic lesions for HSPPC-96 production. HSPPC-96 was administered subcutaneously (s.c.) in four weekly intervals (first cycle). Patients with more available vaccine and absence of progressive disease received four additional injections in 2-week intervals (second cycle) or more. GM-CSF was given s.c. at the same site at days -1, 0 and +1, while IFN-alpha (3 MU) was administered s.c. at a different site at days +4 and +6. Antigen-specific anti-melanoma T and NK lymphocyte response was assessed by enzyme-linked immunospot assay on peripheral blood mononuclear cells obtained before and after vaccination. Thirty-eight patients were enrolled, 20 received at least four injections (one cycle) of HSPPC-96 and were considered assessable. Toxicity was mild and most treatment-related adverse events were local erythema and induration at the injection site. Patients receiving at least four injections of HSPPC-96 were considered evaluable for clinical response: of the 18 patients with measurable disease post surgery, 11 showed stable disease (SD). The ELISPOT assay revealed an increased class I HLA-restricted T and NK cell-mediated post-vaccination response in 5 out of 17 and 12 out of the 18 patients tested, respectively. Four of the five class I HLA-restricted T cell responses fall in the group of SD patients. Vaccination with autologous HSPPC-96 together with GM-CSF and IFN-alpha is feasible and accompanied by mild local and systemic toxicity. Both tumor-specific T cell-mediated and NK cell responses were generated in a proportion of patients. Clinical activity was limited to SD. However, both immunological and clinical responses were not improved as compared with those recorded in a previous study investigating HSPPC-96 monotherapy.
authors.affiliation: Unit of Immunotherapy of Human Tumors, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pilla
authors.forename: Roberto
authors.initials: R
authors.lastname: Patuzzo
authors.forename: Licia
authors.initials: L
authors.lastname: Rivoltini
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pennacchioli
authors.forename: Elda
authors.initials: E
authors.lastname: Lamaj
authors.forename: Andrea
authors.initials: A
authors.lastname: Maurichi
authors.forename: Samuele
authors.initials: S
authors.lastname: Massarut
authors.forename: Alfonso
authors.initials: A
authors.lastname: Marchianò
authors.forename: Cristina
authors.initials: C
authors.lastname: Santantonio
authors.forename: Diego
authors.initials: D
authors.lastname: Tosi
authors.forename: Flavio
authors.initials: F
authors.lastname: Arienti
authors.forename: Agata
authors.initials: A
authors.lastname: Cova
authors.forename: Gloria
authors.initials: G
authors.lastname: Sovena
authors.forename: Adriano
authors.initials: A
authors.lastname: Piris
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nonaka
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bersani
authors.forename: Annabella
authors.initials: A
authors.lastname: Di Florio
authors.forename: Mariani
authors.initials: M
authors.lastname: Luigi
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Srivastava
authors.forename: Axel
authors.initials: A
authors.lastname: Hoos
authors.forename: Mario
authors.initials: M
authors.lastname: Santinami
authors.forename: Giorgio
authors.initials: G
authors.lastname: Parmiani
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000627:therapeutic use*; D015234:HLA-A Antigens / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D015234:HLA-A Antigens; D006360:Heat-Shock Proteins; D016898:Interferon-alpha; C484813:vitespin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor