title: Immunologic analysis of a phase I/II study of vaccination with MAGE-3 protein combined with the AS02B adjuvant in patients with MAGE-3-positive tumors.
abstract: In a phase I/II study, patients with solid metastatic MAGE-3-positive tumors, mainly melanoma, were vaccinated with recombinant MAGE-3 protein combined with the immunologic adjuvant AS02B comprised of MPL and QS21 in an oil-in-water emulsion. The recombinant MAGE-3 protein was made up of a partial sequence of the protein D (ProtD) antigen of Haemophilus influenzae fused to the MAGE-3 sequence. The vaccine was given intramuscularly at 3-week intervals. Patients whose tumors stabilized or regressed after 4 vaccinations received 2 additional vaccinations at 6-week intervals. MAGE-3 and ProtD antibody and cellular immune responses were monitored after vaccination. Ninety-six percent (23/24) of the patients vaccinated with MAGE-3 protein in AS02B adjuvant elicited a significant anti-MAGE-3 IgG antibody response after 4 vaccinations, and all developed anti-ProtD IgG antibodies. For the detection of T-cell activity, total peripheral blood mononuclear cells were restimulated in vitro with MAGE-3- or ProtD-loaded autologous mature dendritic cells. In 30% of the evaluable patients vaccinated with the adjuvanted recombinant protein, IFNgamma production was increased in response to MAGE-3, and 2 patients (14% of evaluable patients) had a concomitant increase in IL-5 production. In 37% and 43% of the patients, respectively, IFNgamma or IL-5 production was increased in response to ProtD. It is concluded that vaccination of advanced cancer patients with MAGE-3 self-antigen in AS02B adjuvant is able to elicit MAGE-3-specific antibody and a T-cell response.
authors.affiliation: GlaxoSmithKline Biologicals, Rixensart, Belgium.
authors.forename: Valérie
authors.initials: V
authors.lastname: Vantomme
authors.forename: Christine
authors.initials: C
authors.lastname: Dantinne
authors.forename: Noreddine
authors.initials: N
authors.lastname: Amrani
authors.forename: Philippe
authors.initials: P
authors.lastname: Permanne
authors.forename: Dirk
authors.initials: D
authors.lastname: Gheysen
authors.forename: Claudine
authors.initials: C
authors.lastname: Bruck
authors.forename: Gerrit
authors.initials: G
authors.lastname: Stoter
authors.forename: Cedrik M
authors.initials: CM
authors.lastname: Britten
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
authors.forename: Cor H J
authors.initials: CH
authors.lastname: Lamers
authors.forename: Marie
authors.initials: M
authors.lastname: Marchand
authors.forename: Marcel
authors.initials: M
authors.lastname: Delire
authors.forename: Maryse
authors.initials: M
authors.lastname: Guéguen
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000737:chemistry; D015153:Blotting, Western; D016466:CHO Cells; D019496:Cancer Vaccines / Q000276:immunology*; D002352:Carrier Proteins / Q000737:chemistry; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000378:metabolism; D006193:Haemophilus influenzae / Q000378:metabolism; D006801:Humans; D007072:Immunoglobulin D / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D007313:Insecta; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008074:Lipoproteins / Q000737:chemistry; D009363:Neoplasm Proteins / Q000627:therapeutic use*; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D001426:Bacterial Proteins; D019496:Cancer Vaccines; D002352:Carrier Proteins; D016207:Cytokines; D007072:Immunoglobulin D; D015848:Interleukin-5; D008074:Lipoproteins; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; C067989:glpQ protein, Haemophilus influenzae