Originally published as JCO Early Release 10.1200/JCO.2005.08.375 on August 1 2005

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Tumoral and Immunologic Response After Vaccination of Melanoma Patients With an ALVAC Virus Encoding MAGE Antigens Recognized by T Cells

Nicolas van Baren, Marie-Claude Bonnet, Brigitte Dréno, Amir Khammari, Thierry Dorval, Sophie Piperno-Neumann, Danielle Liénard, Daniel Speiser, Marie Marchand, Vincent G. Brichard, Bernard Escudier, Sylvie Négrier, Pierre-Yves Dietrich, Dominique Maraninchi, Susanne Osanto, Ralf G. Meyer, Gerd Ritter, Philippe Moingeon, Jim Tartaglia, Pierre van der Bruggen, Pierre G. Coulie, Thierry Boon

From the Ludwig Institute for Cancer Research, Brussels Branch; Génétique Cellulaire, Université de Louvain; Centre du Cancer, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Aventis Pasteur, Lyon; Hôtel-Dieu, Centre Hospitalier Universitaire de Nantes; Institut Curie, Paris; Institut Gustave-Roussy, Villejuif; Centre Léon Bérard, Lyon; Institut Paoli-Calmettes, Marseille, France; Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne; Hôpital Cantonal Universitaire, Genève, Switzerland; Leiden University Medical Center, Leiden, the Netherlands; Johannes Gutenberg University, Mainz, Germany; Ludwig Institute for Cancer Research, New York Branch, New York, NY; and Aventis Pasteur, Toronto, Ontario, Canada

Address reprint requests to N. van Baren, Ludwig Institute for Cancer Research, 74 avenue Hippocrate, UCL7459, B-1200 Brussels, Belgium; e-mail: nicolas.vanbaren{at}bru.licr.org.

PURPOSE: To evaluate the toxicity, antitumoral effectiveness, and immunogenicity of repeated vaccinations with ALVAC miniMAGE-1/3, a recombinant canarypox virus containing a minigene encoding antigenic peptides MAGE-3_168-176 and MAGE-1_161-169, which are presented by HLA-A1 and B35 on tumor cells and can be recognized by cytolytic T lymphocytes (CTLs).

MATERIALS AND METHODS: The vaccination schedule comprised four sequential injections of the recombinant virus, followed by three booster vaccinations with the MAGE-3_168-176 and MAGE-1_161-169 peptides. The vaccines were administered, both intradermally and subcutaneously, at 3-week intervals.

RESULTS: Forty patients with advanced cancer were treated, including 37 melanoma patients. The vaccines were generally well tolerated with moderate adverse events, consisting mainly of transient inflammatory reactions at the virus injection sites. Among the 30 melanoma patients assessable for tumor response, a partial response was observed in one patient, and disease stabilization in two others. The remaining patients had progressive disease. Among the patients with stable or progressive disease, five showed evidence of tumor regression. A CTL response against the MAGE-3 vaccine antigen was detected in three of four patients with tumor regression, and in only one of 11 patients without regression.

CONCLUSION: Repeated vaccination with ALVAC miniMAGE-1/3 is associated with tumor regression and with a detectable CTL response in a minority of melanoma patients. There is a significant correlation between tumor regression and CTL response. The contribution of vaccine-induced CTL in the tumor regression process is discussed in view of the immunologic events that could be analyzed in detail in one patient.

Supported by Aventis Pasteur, Lyon, France

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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