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.
|Keywords||Animals, Antigens, Neoplasm/*therapeutic use, Bacterial Proteins/chemistry, Blotting, Western, CHO Cells, Cancer Vaccines/*immunology, Carrier Proteins/chemistry, Cricetinae, Cytokines/biosynthesis/metabolism, Dendritic Cells/metabolism, Escherichia coli/metabolism, Haemophilus influenzae/metabolism, Humans, Immunoglobulin D/chemistry, Immunotherapy/*methods, Insects, Interferon-gamma/metabolism, Interleukin-5/metabolism, Leukocytes, Mononuclear/metabolism, Lipoproteins/chemistry, Neoplasm Proteins/*therapeutic use, Neoplasms/*immunology/metabolism, Recombinant Fusion Proteins/chemistry, T-Lymphocytes/metabolism, Time Factors, Treatment Outcome|
Vantomme, V., Dantinne, C., Amrani, N., Permanne, P., Gheysen, D., Bruck, C., … Guéguen, M.. (2004). 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. Journal of Immunotherapy, 27(2), 124–135. Retrieved from http://hdl.handle.net/1765/21342