Vaccination of Metastatic Melanoma Patients With Autologous Tumor-Derived Heat Shock Protein gp96-Peptide Complexes: Clinical and Immunologic Findings
-
Published:2002-10-15
Issue:20
Volume:20
Page:4169-4180
-
ISSN:0732-183X
-
Container-title:Journal of Clinical Oncology
-
language:en
-
Short-container-title:JCO
Author:
Belli Filiberto1, Testori Alessandro1, Rivoltini Licia1, Maio Michele1, Andreola Giovanna1, Sertoli Mario Roberto1, Gallino Gianfrancesco1, Piris Adriano1, Cattelan Alessandro1, Lazzari Ivano1, Carrabba Matteo1, Scita Giorgio1, Santantonio Cristina1, Pilla Lorenzo1, Tragni Gabrina1, Lombardo Claudia1, Arienti Flavio1, Marchianò Alfonso1, Queirolo Paola1, Bertolini Francesco1, Cova Agata1, Lamaj Elda1, Ascani Lucio1, Camerini Roberto1, Corsi Marco1, Cascinelli Natale1, Lewis Jonathan J.1, Srivastava Pramod1, Parmiani Giorgio1
Affiliation:
1. From the Units of General Surgery 2, Immunotherapy of Human Tumors, Immunohematology and Blood Bank, Pathology, Diagnostic Radiology, and Pharmacy, Istituto Nazionale Tumori; Divisions of Surgery and Pathology, Istituto Europeo di Oncologia, Milan; Units of Cancer Biotherapy, Anesthesiology, and Surgery, Centro di Riferimento Oncologico, Aviano; Divisions of Medical Oncology and Surgery, Istituto Scientifico Tumori, Genoa; and Sigma Tau, i.f.r. S.p.A., Rome, Italy; Antigenics, Inc, Woburn, MA; and Center...
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.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Reference33 articles.
1. Legha SS, Ring S, Eton O, et al: Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma. J Clin Oncol 16: 1752,1999-1759, 2. Sequential Biochemotherapy Versus Chemotherapy for Metastatic Melanoma: Results From a Phase III Randomized Trial 3. Prospective Randomized Trial of the Treatment of Patients With Metastatic Melanoma Using Chemotherapy With Cisplatin, Dacarbazine, and Tamoxifen Alone or in Combination With Interleukin-2 and Interferon Alfa-2b 4. Vaccination of melanoma patients with peptide- or tumorlysate-pulsed dendritic cells 5. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by geneMAGE-3 and presented by HLA-A1
Cited by
328 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|