通过鉴定出一种自组装的小分子癌症疫苗佐剂,并改善了其毒性特征。
Identification of a Self-Assembling Small-Molecule Cancer Vaccine Adjuvant with an Improved Toxicity Profile.
发表日期:2023 Sep 07
作者:
Shao-Hua Zhuo, Naotaka Noda, Kou Hioki, Shuyu Jin, Tomoya Hayashi, Kou Hiraga, Haruka Momose, Wen-Hao Li, Lang Zhao, Takuo Mizukami, Ken J Ishii, Yan-Mei Li, Motonari Uesugi
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
蛋白质或多肽癌症疫苗通常包括免疫增强剂,即所谓的佐剂。然而,要找到结构简单、化学易获得、安全并有效的疫苗佐剂仍然具有挑战性。在这里,我们介绍了胆寡胺β(6),一种自组装的小分子疫苗佐剂,其毒性改善,并且在体内已被证明具有疗效。我们证明了胆寡胺β(6)不如其母化合物细胞毒性低,形成病毒样颗粒,能够强烈激活树突状细胞并伴随细胞因子的分泌。当与多肽抗原结合时,胆寡胺β(6)能够增强树突状细胞上的抗原呈递,诱导特异性抗原T细胞的产生。作为小鼠治疗性癌症疫苗佐剂,胆寡胺β(6)与多肽抗原的混合物能够保护小鼠免受恶性癌细胞的侵袭,而没有明显的毒性。胆寡胺β(6)可能为一种前所未有的小分子癌症疫苗佐剂提供了转化机会。
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.