title: Phase 1/2 study of subcutaneous and intradermal immunization with a recombinant MAGE-3 protein in patients with detectable metastatic melanoma.
abstract: 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.
authors.affiliation: Erasmus Medical Center-Daniel den Hoed Cancer Center, Department of Internal Oncology, Rotterdam, The Netherlands.
authors.forename: Wim H J
authors.initials: WH
authors.lastname: Kruit
authors.forename: Heidi H
authors.initials: HH
authors.lastname: van Ojik
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Brichard
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.forename: Thierry
authors.initials: T
authors.lastname: Dorval
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dréno
authors.forename: Poulam
authors.initials: P
authors.lastname: Patel
authors.forename: Nicolas
authors.initials: N
authors.lastname: van Baren
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
authors.forename: Sophie
authors.initials: S
authors.lastname: Piperno
authors.forename: Amir
authors.initials: A
authors.lastname: Khammari
authors.forename: Marguerite
authors.initials: M
authors.lastname: Stas
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Bernard
authors.initials: B
authors.lastname: Lethé
authors.forename: Danièle
authors.initials: D
authors.lastname: Godelaine
authors.forename: Francis
authors.initials: F
authors.lastname: Brasseur
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Pierre
authors.initials: P
authors.lastname: van der Bruggen
authors.forename: Thierry
authors.initials: T
authors.lastname: Boon
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Marie
authors.initials: M
authors.lastname: Marchand
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D011994:Recombinant Proteins