Identification of a Self-Assembling Small-Molecule Cancer Vaccine Adjuvant with an Improved Toxicity Profile

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.