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

被引:76
作者
Vantomme, V
Dantinne, C
Amrani, N
Permanne, P
Gheysen, D
Bruck, C
Stoter, G
Britten, CM
Keilholz, U
Lamers, CHJ
Marchand, M
Delire, M
Guéguen, M
机构
[1] GlaxoSmithKline Biol, B-1330 Rixensart, Belgium
[2] Rotterdam Canc Inst, Rotterdam, Netherlands
[3] Johannes Gutenberg Univ Mainz, D-6500 Mainz, Germany
[4] Free Univ Berlin, Univ Hosp Benjamin Franklin, Dept Med 3, Berlin, Germany
[5] Dr Daniel Den Hoed Canc Ctr, NL-3008 AE Rotterdam, Netherlands
[6] Ludwig Inst Canc Res, Brussels Branch, Brussels, Belgium
[7] Univ Louvain, Clin Univ St Luc, Brussels, Belgium
关键词
cancer immunotherapy; tumor antigen; humoral and cellular response;
D O I
10.1097/00002371-200403000-00006
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:124 / 135
页数:12
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