Identification of a Self-Assembling Small-Molecule Cancer Vaccine Adjuvant with an Improved Toxicity Profile.
Shao-Hua ZhuoNaotaka NodaKou HiokiShuyu JinTomoya HayashiKou HiragaHaruka MomoseWen-Hao LiLang ZhaoTakuo MizukamiKen J IshiiYan-Mei LiMotonari UesugiPublished in: Journal of medicinal chemistry (2023)
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 ( 6 ), a self-assembling small-molecule vaccine adjuvant with an improved toxicity profile and proven efficacy in vivo . We demonstrate that cholicamideβ ( 6 ), 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 ( 6 ) 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 ( 6 ) and a peptide antigen protected mice from the challenges of malignant cancer cells without overt toxicity. Cholicamideβ ( 6 ) may offer a translational opportunity as an unprecedented class of small-molecule cancer vaccine adjuvants.