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

Vantomme, Valérie;Dantinne, Christine;Amrani, Noreddine;Permanne, Philippe;Gueguen, Maryse;et.al.
(2004) Journal Of Immunotherapy — Vol. 27, n° 2, p. 124-135 (2004)

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Authors
  • Vantomme, Valérie
    Author
  • Dantinne, Christine
    Author
  • Amrani, Noreddine
    Author
  • Permanne, Philippe
    Author
  • Marchand, MarieUCLouvain
    Author
  • Gueguen, Maryse
    Author
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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.
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Citations

Vantomme, V., Dantinne, C., Amrani, N., Permanne, P., Gheysen, D., Bruck, C., Stoter, G., Britten, C. M., Keilholz, U., Lamers, C. H., Marchand, M., Delire, M., & Gueguen, 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. https://doi.org/10.1097/00002371-200403000-00006 (Original work published 2004)