Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: Clinical and immunologic findings

Filiberto Belli, Alessandro Testori, Licia Rivoltini, Michele Maio, Giovanna Andreola, Mario Roberto Sertoli, Gianfrancesco Gallino, Adriano Piris, Alessandro Cattelan, Ivano Lazzari, Matteo Carrabba, Giorgio Scita, Cristina Santantonio, Lorenzo Pilla, Gabrina Tragni, Claudia Lombardo, Flavio Arienti, Alfonso Marchianò, Paola Queirolo, Francesco BertoliniAgata Cova, Elda Lamaj, Lucio Ascani, Roberto Camerini, Marco Corsi, Natale Cascinelli, Jonathan J. Lewis, Pramod Srivastava, Giorgio Parmiani

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: 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. Patients and 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)4169-4180
Number of pages12
JournalJournal of Clinical Oncology
Volume20
Issue number20
DOIs
Publication statusPublished - Oct 15 2002

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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