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Phase 1/2 study of subcutaneous and intradermal immunization with a recombinant MAGE-3 protein in patients with detectable metastatic melanoma

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Kruit, WHJ Van Ojik, Heidi H. Brichard, Vincent G. [UCL] Escudier, B Dorval, T van Baren, Nicolas [UCL] LETHE, Bernard [UCL] GODELAINE, Danièle [UCL] Brasseur, Francis [UCL] Zhang, Yi [UCL] van der Bruggen, Pierre [UCL] Boon, Thierry [UCL] Marchand, Marie [UCL]

The purpose of this phase 1/2 study was to evaluate toxicity, tumor evolution and immunologic response following administration of a fixed dose of a recombinant MAGE-3 protein by subcutaneous and intradermal routes in the absence of immunologic adjuvant. Thirty-two patients with detectable metastatic melanoma expressing gene MAGE-3 were included and 30 received at least one injection with a fixed dose of a ProtD-MAGE-3 fusion protein. The immunization schedule included 6 intradermal and subcutaneous injections at 3-week intervals. Afterward, patients without major tumor progression who required other treatments received additional vaccinations at increasing time intervals. The vaccine was generally well tolerated. Among the 26 patients who received at least 4 vaccinations, we observed 1 partial response and 4 mixed responses. For these 5 responding patients, time to progression varied from 3.5 to 51+ months. An anti-MAGE-3 CD4 T-lymphocyte response was detected in 1 out of the 5 responding patients. The majority of patients had no anti-MAGE-3 antibody response. The clinical and immunologic responses generated by the vaccine are rather limited. Nevertheless, given the potential antitumor efficacy and the very mild toxicity of vaccinations, further studies combining MAGE proteins and/or peptides with potent immunologic adjuvants are warranted, not only in metastatic melanoma, but also in the adjuvant setting. (c) 2005 Wiley-Liss, Inc.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2005
Language Anglais
Journal information "International Journal of Cancer" - Vol. 117, no. 4, p. 596-604 (2005)
Peer reviewed yes
Publisher Wiley-liss (Hoboken)
issn 0020-7136
e-issn 1097-0215
Publication status Publié
Affiliations UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique
UCL - MD/MINT - Département de médecine interne
UCL - (SLuc) Unité d'oncologie médicale
UCL - (SLuc) Service d'hématologie
UCL - (SLuc) Centre du cancer
MESH Subject Survival Analysis ; Recombinant Proteins - administration & dosage - adverse effects - therapeutic use ; Neoplasm Proteins - administration & dosage - adverse effects - therapeutic use ; Neoplasm Metastasis ; Middle Aged ; Melanoma - drug therapy - immunology - pathology ; Male ; Injections, Subcutaneous ; Humans ; Female ; Disease Progression ; CD4-Positive T-Lymphocytes - immunology ; Antigens, Neoplasm - administration & dosage - adverse effects - therapeutic use ; Aged, 80 and over ; Aged ; Adult
Keywords MAGE-3 ; melanoma ; protein ; T lymphocyte ; vaccine
Links
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Bibliographic reference Kruit, WHJ ; Van Ojik, Heidi H. ; Brichard, Vincent G. ; Escudier, B ; Dorval, T ; et. al. Phase 1/2 study of subcutaneous and intradermal immunization with a recombinant MAGE-3 protein in patients with detectable metastatic melanoma. In: International Journal of Cancer, Vol. 117, no. 4, p. 596-604 (2005)
Permanent URL http://hdl.handle.net/2078.1/39049