Key Laboratory of Pesticide & Chemical Biology of 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, China.
Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, East China University of Technology, Nanchang, Jiangxi, 330013, China.
Chem Asian J. 2019 Jun 14;14(12):2116-2121. doi: 10.1002/asia.201900448. Epub 2019 May 21.
The tumor-associated antigen mucin 1 (MUC1) has been pursued as an attractive target for cancer immunotherapy, but the poor immunogenicity of the endogenous antigen hinders the development of vaccines capable of inducing effective anti-MUC1 immunodominant responses. Herein, we prepared synthetic anti-MUC1 vaccines in which the hydrophilic MUC1 antigen was N-terminally conjugated to one or two palmitoyl lipid chains (to form amphiphilic Pam-MUC1 or Pam -MUC1). These amphiphilic lipid-tailed MUC1 antigens were self-assembled into liposomes containing the NKT cell agonist αGalCer as an adjuvant. The lipid-conjugated antigens reshaped the physical and morphological properties of liposomal vaccines. Promising results showed that the anti-MUC1 IgG antibody titers induced by the Pam -MUC1 vaccine were more than 30- and 190-fold higher than those induced by the Pam-MUC1 vaccine and the MUC1 vaccine without lipid tails, respectively. Similarly, vaccines with the TLR1/2 agonist Pam CSK as an adjuvant also induced conjugated lipid-dependent immunological responses. Moreover, vaccines with the αGalCer adjuvant induced significantly higher titers of IgG antibodies than vaccines with the Pam CSK adjuvant. Therefore, the non-covalent assembly of the amphiphilic lipo-MUC1 antigen and the NKT cell agonist αGalCer as a glycolipid adjuvant represent a synthetically simple but immunologically effective approach for the development of anti-MUC1 cancer vaccines.
肿瘤相关抗原黏蛋白 1（MUC1）一直被作为癌症免疫治疗的一个有吸引力的靶点，但其内源性抗原的免疫原性较差，阻碍了能够诱导有效抗 MUC1 免疫优势反应的疫苗的发展。在此，我们制备了合成的抗 MUC1 疫苗，其中亲水的 MUC1 抗原通过 N 端与一个或两个棕榈酰脂质链连接（形成两亲性 Pam-MUC1 或 Pam -MUC1）。这些两亲性脂质尾巴的 MUC1 抗原自组装成含有 NKT 细胞激动剂 αGalCer 的脂质体作为佐剂。脂质偶联的抗原重塑了脂质体疫苗的物理和形态特性。有希望的结果表明，Pam -MUC1 疫苗诱导的抗 MUC1 IgG 抗体滴度分别比 Pam-MUC1 疫苗和没有脂质尾巴的 MUC1 疫苗诱导的滴度高 30 倍和 190 倍。同样，用 TLR1/2 激动剂 Pam CSK 作为佐剂的疫苗也诱导了与共轭脂质相关的免疫反应。此外，用αGalCer 佐剂的疫苗诱导的 IgG 抗体滴度明显高于用 Pam CSK 佐剂的疫苗。因此，将两亲性 lipo-MUC1 抗原与 NKT 细胞激动剂 αGalCer 非共价组装作为糖脂佐剂代表了一种合成简单但免疫有效的方法，用于开发抗 MUC1 癌症疫苗。
