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.
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.
Vantomme
Valérie
V
GlaxoSmithKline Biologicals, Rixensart, Belgium.
Dantinne
Christine
C
Amrani
Noreddine
N
Permanne
Philippe
P
Gheysen
Dirk
D
Bruck
Claudine
C
Stoter
Gerrit
G
Britten
Cedrik M
CM
Keilholz
Ulrich
U
Lamers
Cor H J
CH
Marchand
Marie
M
Delire
Marcel
M
Guéguen
Maryse
M
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
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