Cancer Immunology, Immunotherapy

, 55:958

A phase II trial of vaccination with autologous, tumor-derived heat-shock protein peptide complexes Gp96, in combination with GM-CSF and interferon-α in metastatic melanoma patients

  • Lorenzo Pilla
  • Roberto Patuzzo
  • Licia Rivoltini
  • Michele Maio
  • Elisabetta Pennacchioli
  • Elda Lamaj
  • Andrea Maurichi
  • Samuele Massarut
  • Alfonso Marchianò
  • Cristina Santantonio
  • Diego Tosi
  • Flavio Arienti
  • Agata Cova
  • Gloria Sovena
  • Adriano Piris
  • Daisuke Nonaka
  • Ilaria Bersani
  • Annabella Di Florio
  • Mariani Luigi
  • Pramod K. Srivastava
  • Axel Hoos
  • Mario Santinami
  • Giorgio Parmiani
Original Article

DOI: 10.1007/s00262-005-0084-8

Cite this article as:
Pilla, L., Patuzzo, R., Rivoltini, L. et al. Cancer Immunol Immunother (2006) 55: 958. doi:10.1007/s00262-005-0084-8

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-α 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-α (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-α 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.

Keywords

VaccinationMetastatic melanomaHeat shock proteinsGM-CSFIFN-αPhase II trial

Abbreviations

AEs

adverse events

DTH

delayed-type hypersensitivity

ELISPOT

enzyme-linked immunospot

GM-CSF

granulocyte/macrophage-colony stimulating factor

HSP

heat shock proteins

HSPPC-96

heat shock proteins peptide complexes gp96

IFN

interferon

IHC

immunohistochemistry

IL

interleukin

NK

natural killer

PBMC

peripheral blood mononuclear cells

RECIST

response evaluation criteria in solid tumors

s.c.

subcutaneously

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Lorenzo Pilla
    • 1
  • Roberto Patuzzo
    • 2
  • Licia Rivoltini
    • 1
  • Michele Maio
    • 3
    • 10
  • Elisabetta Pennacchioli
    • 2
  • Elda Lamaj
    • 3
  • Andrea Maurichi
    • 2
  • Samuele Massarut
    • 3
  • Alfonso Marchianò
    • 4
  • Cristina Santantonio
    • 3
  • Diego Tosi
    • 1
  • Flavio Arienti
    • 5
  • Agata Cova
    • 1
  • Gloria Sovena
    • 1
  • Adriano Piris
    • 6
  • Daisuke Nonaka
    • 6
  • Ilaria Bersani
    • 1
  • Annabella Di Florio
    • 1
  • Mariani Luigi
    • 7
  • Pramod K. Srivastava
    • 8
  • Axel Hoos
    • 9
  • Mario Santinami
    • 2
  • Giorgio Parmiani
    • 1
  1. 1.Unit of Immunotherapy of Human TumorsIstituto Nazionale per lo Studio e la Cura dei TumoriMilanItaly
  2. 2.Unit of Melanoma and Sarcoma SurgeryIstituto Nazionale per lo Studio e la Cura dei TumoriMilanItaly
  3. 3.Centro di Riferimento OncologicoAvianoItaly
  4. 4.Unit of RadiologyIstituto Nazionale per lo Studio e la Cura dei TumoriMilanItaly
  5. 5.Unit of ImmunohematologyIstituto Nazionale per lo Studio e la Cura dei TumoriMilanItaly
  6. 6.Unit of PathologyIstituto Nazionale per lo Studio e la Cura dei TumoriMilanItaly
  7. 7.Unit of Medical Statistics and BiometryIstituto Nazionale per lo Studio e la Cura dei TumoriMilanItaly
  8. 8.Department of Microbiology and ImmunologyUniversity of ConnecticutFarmingtonUSA
  9. 9.Antigenics Inc.LexingtonUSA
  10. 10.Unit of Medical Oncologic and Immunotherapy, Department of OncologyAzienda Ospedaliera Universitaria SeneseSienaItaly