Protein or peptide cancer vaccines usually include immune potentiators, so-called adjuvants. However, it remains challenging to identify structurally simple, chemically accessible synthetic molecules that are effective and safe as vaccine adjuvant. Here, we present cholicamideβ (), a self-assembling small-molecule vaccine adjuvant with an improved toxicity profile and proven efficacy . We demonstrate that cholicamideβ (), which is less cytotoxic than its parent compound, forms virus-like particles to potently activate dendritic cells with the concomitant secretion of cytokines. When combined with a peptide antigen, cholicamideβ () potentiated the antigen presentation on dendritic cells to induce antigen-specific T cells. As a therapeutic cancer vaccine adjuvant in mice, a mixture of cholicamideβ () and a peptide antigen protected mice from the challenges of malignant cancer cells without overt toxicity. Cholicamideβ () may offer a translational opportunity as an unprecedented class of small-molecule cancer vaccine adjuvants.
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