Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079, P. R. China.
J Med Chem. 2021 Feb 25;64(4):1951-1965. doi: 10.1021/acs.jmedchem.0c01186. Epub 2021 Feb 4.
GM3, a typical tumor-associated carbohydrate antigen, is considered as an important target for cancer vaccine development, but its low immunogenicity limits its application. αGalCer, an iNKT cell agonist, has been employed as an adjuvant via a unique immune mode. Herein, we prepared and investigated two types of antitumor vaccine candidates: (a) self-adjuvanting vaccine by conjugating GM3 with αGalCer and (b) noncovalent vaccine , in which GM3 is linked with lipid anchor and coassembled with αGalCer. This demonstrated that βGalCer is an exceptionally optimized lipid anchor, which enables the noncovalent vaccine candidate to evoke a comparable antibody level to . However, the antibodies induced by are better at recognition B16F10 cancer cells and more effectively activate the complement system. Our study highlights the importance of vaccine constructs utilizing covalent or noncovalent assembly between αGalCer with carbohydrate antigens and choosing an appropriate lipid anchor for use in noncovalent vaccine formulation.
GM3 是一种典型的肿瘤相关碳水化合物抗原，被认为是癌症疫苗开发的重要靶点，但它的免疫原性较低限制了其应用。αGalCer 是一种 iNKT 细胞激动剂，已通过独特的免疫模式被用作佐剂。在此，我们制备并研究了两种类型的抗肿瘤疫苗候选物：（a）通过将 GM3 与 αGalCer 缀合制备的自佐剂疫苗，和（b）非共价疫苗，其中 GM3 通过脂质锚链接并与 αGalCer 共组装。这表明βGalCer 是一种特别优化的脂质锚，使非共价疫苗候选物 能够引发与 相当的抗体水平。然而，由 诱导的抗体更善于识别 B16F10 癌细胞，并更有效地激活补体系统。我们的研究强调了利用 αGalCer 与碳水化合物抗原之间的共价或非共价组装构建疫苗的重要性，以及在非共价疫苗配方中选择合适的脂质锚的重要性。
