Journal Article

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

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

2006

Overview

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.

• Publisher: Springer,Springer Nature B.V,Springer-Verlag
• Subject: Adjuvants, Immunologic - therapeutic use / Adult / Aged / Antineoplastic agents / Antitumor activity / Biological and medical sciences / Cancer Vaccines - immunology / Cancer Vaccines - therapeutic use / Dermatology / Enzyme-linked immunosorbent assay / Erythema / Female / Glycoprotein gp96 / Granulocyte-macrophage colony-stimulating factor / Granulocyte-Macrophage Colony-Stimulating Factor - immunology / Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use / Heat shock proteins / Heat-Shock Proteins - immunology / Heat-Shock Proteins - therapeutic use / Histocompatibility antigen HLA / HLA-A Antigens - immunology / Humans / Immunization / Immunogenicity / Immunotherapy / Injections / Interferon-alpha - immunology / Interferon-alpha - therapeutic use / Killer Cells, Natural - immunology / Leukocytes (mononuclear) / Lymphocytes T / Male / Medical sciences / Melanoma / Melanoma - immunology / Melanoma - therapy / Metastases / Metastasis / Middle Aged / Natural killer cells / Original / Patients / Peptides / Peripheral blood mononuclear cells / Pharmacology. Drug treatments / T-Lymphocytes - immunology / Toxicity / Treatment Outcome / Tumors / Tumors of the skin and soft tissue. Premalignant lesions / Vaccines / α-Interferon