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Identification of a Self-Assembling Small-Molecule Cancer Vaccine Adjuvant with an Improved Toxicity Profile
- Source :
- Journal of Medicinal Chemistry; 20230101, Issue: Preprints
- Publication Year :
- 2023
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 00222623 and 15204804
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Journal of Medicinal Chemistry
- Publication Type :
- Periodical
- Accession number :
- ejs63857346
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.3c01252