Comparison of the immunogenicity of Montanide ISA 51 adjuvant and cytokine-matured dendritic cells in a randomized controlled clinical trial of melanoma vaccines

Abstract

3002 Background: Dendritic cell (DC) vaccines have been widely used in clinical trials to treat cancer. However, no study has compared the immunogenicity of the most commonly used DC type (cytokine-matured, monocyte-derived DCs) to more traditional vaccine adjuvants. We performed a randomized controlled trial comparing the immunogenicity of cytokine-matured DCs loaded with 6 HLA-A2-restricted peptide antigens and a foreign protein, KLH, to a vaccine containing the same antigens emulsified in the mineral oil adjuvant Montanide ISA 51 VG. Methods: 51 HLA-A2+ patients with resected stage IIb-IIIc melanoma were randomized to receive DCs (25 patients) or Montanide (26 patients). DCs were differentiated from autologous blood monocytes with IL-4 and GM-CSF, then matured with IL- 1β, IL-6, TNFα and PGE2. 18 million DCs were given i.d. every 4 weeks x 4, and immune responses analyzed (MHC multimers, T cell proliferation, cytokine secretion, antibodies). A 3-fold increase over baseline was considered a response. Results: Both vaccines were well tolerated. Immunogenicity was significantly greater with Montanide, as demonstrated by response rates to Flu, Melan-A and NY-ESO-1 peptides by IFNγ ELISPOT. Similar results were obtained by MHC multimer staining, with higher response rates seen using pre-sensitized assays. T cell proliferation to KLH was seen in both arms (90% DC, 100% Montanide), but the magnitude of response was significantly higher for Montanide (36-fold vs. 14-fold increase over baseline, p=0.002, Wilcoxon). KLH-specific CD4+ T cells that produced IFNγ, TNFα and IL-2 were seen only with Montanide, and all Montanide patients, but only 5% of DC patients, developed antibodies to KLH (p<0.001, Fisher's). Conclusions: A water-in-oil vaccine adjuvant, Montanide ISA 51, was significantly more immunogenic than DCs. Future studies of new DC vaccines should compare DCs to standard adjuvants to determine if their added difficulty and expense are truly warranted. [Table: see text] [Table: see text]