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• W2284668836 abstract "2526 Background: The MAGE-A3 gene codes for tumor-specific antigens recognized by CD4+ and CD8+ T-cells. We and others previously reported trials with HLA class I-peptide loaded on autologous dendritic cells (DC) that induced specific T cells and occasional antitumor responses. This immune response was transient, possibly due to the lack of T-cell help. Here, we evaluated the potential advantage of the concurrent presentation of CD4+ and CD8+ epitopes on the recombinant (rec) MAGE-A3 protein loaded on myeloid DC, as compared to the protein combined with adjuvant AS02B. Methods: 19 patients (pts) with evaluable stage III or IV MAGE-A3 expressing melanoma received 4 vaccines (weeks 0, 2, 6, 10) of recMAGE-A3 protein either loaded on autologous non-mature DC (40–100 x 10E6 i.d./s.c.), or mixed with AS02B adjuvant (adj.) (300 μg of protein i.m.). DC were generated from adherent PBMC for 7 days with GM-CSF + IL-4, then pulsed with the protein for 1h. T-cell response was analyzed by Elispot after in vitro restimulation, and Ab response by ELISA. Additional compassionate vaccines (rec protein) were given in case of clinical benefit. Results: From the 19 pts, 18 were eligible and, among them, 14 received the 4 vaccines (3 rapid progressions and 1 technical problem). In both arms, no serious toxicity was reported. We observed in the adj. arm (9 pts): one partial response (7 mo), one mixed response (>34mo, with vitiligo surrounding a responsive lesion), and one stable disease (>26mo); in the DC arm (5 pts): one mixed response (>23mo). Pts showed a strong Ab response against the protein in the adj. arm, while no Ab was detected in the DC arm. Moreover, increase in anti-MAGE-A3 T cell frequency (defined as a minimum of 2.5x baseline frequency) was detected in 4 out of 9 pts in adj. arm, and in 1 out of 5 pts in DC arm (responders: n=5, mean fold increase baseline = 9.7). All but one pt with clinical responses were in the T cell responder group. Conclusions: Vaccines with recMAGE-A3 protein given with AS02B adjuvant or loaded on DC were safe. Although the cohorts are small, clinical and immune responses against MAGE-A3 protein seem to be more frequent in the AS02B adjuvant arm than in the non-mature DC arm. No significant financial relationships to disclose." @default.
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• W2284668836 date "2005-06-01" @default.
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• W2284668836 title "A randomized phase I/II trial of antitumor vaccination using the recombinant MAGE-A3 protein loaded on myeloid DC or mixed with adjuvant ASO2B in melanoma patients" @default.
• W2284668836 doi "https://doi.org/10.1200/jco.2005.23.16_suppl.2526" @default.
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