Synthesis and Evaluation of Liposomal Anti-GM3 Cancer Vaccine Candidates Covalently and Noncovalently Adjuvanted by αGalCer

Xu-Guang  Yin; Jie  Lu; Jian  Wang; Ru-Yan  Zhang; Xi-Feng  Wang; Chun-Miao  Liao; Xiao-Peng  Liu; Zheng  Liu; Jun  Guo

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Synthesis and Evaluation of Liposomal Anti-GM3 Cancer Vaccine Candidates Covalently and Noncovalently Adjuvanted by αGalCer

机译：通过αGalcer共价和非共价佐剂的脂质体抗GM3癌疫苗候选物的合成与评价

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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 GM3-αGalCer by conjugating GM3 with αGalCer and (b) noncovalent vaccine GM3-lipid/αGalCer , 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 GM3-βGalCer/αGalCer to evoke a comparable antibody level to GM3-αGalCer . However, the antibodies induced by GM3-αGalCer 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.

机译：GM3是一种典型的肿瘤相关糖类抗原，被认为是肿瘤疫苗开发的重要靶点，但其低免疫原性限制了其应用。α-GalCer是一种iNKT细胞激动剂，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候选疫苗：（a）通过将GM3与αGalCer结合而制备的自佐剂疫苗GM3-αGalCer；（b）非共价疫苗GM3脂质/αGalCer，其中GM3与脂质锚定连接并与αGalCer共组装。这表明β-GalCer是一种非常优化的脂质锚定物，它使非共价候选疫苗GM3-β-GalCer/α-GalCer能够产生与GM3-α-GalCer相当的抗体水平。然而，GM3-αGalCer诱导的抗体更能识别B16F10癌细胞，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，以及选择合适的脂质锚用于非共价疫苗配方的重要性。

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来源
《Journal of Medicinal Chemistry》 |2021年第4期|共15页
作者
Xu-Guang Yin; Jie Lu; Jian Wang; Ru-Yan Zhang; Xi-Feng Wang; Chun-Miao Liao; Xiao-Peng Liu; Zheng Liu; Jun Guo;
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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;

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;

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;

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;

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;

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;

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;

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;

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;

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Synthesis and Evaluation of Liposomal Anti-GM3 Cancer Vaccine Candidates Covalently and Noncovalently Adjuvanted by αGalCer

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