Liposomal Antitumor Vaccines Targeting Mucin 1 Elicit a Lipid-Dependent Immunodominant Response.

Abstract

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 Pam2 -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 Pam2 -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 Pam3 CSK4 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 Pam3 CSK4 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.

• Authors: Jing-Jing Du, Shi-Yao Zou, Xiang-Zhao Chen, Wen-Bo Xu, Chang-Wei Wang, Lian Zhang, Yuan-Kai Tang, Shi-Hao Zhou, Jian Wang, Xu-Guang Yin, Xiao-Fei Gao, Zheng Liu, Jun Guo
• Journal: Chemistry, an Asian journal (Chem Asian J) Vol. 14 Issue 12 Pg. 2116-2121 (Jun 14 2019) ISSN: 1861-471X [Electronic] Germany
• PMID: 31042017 (Publication Type: Journal Article)
• Copyright: © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Cancer Vaccines
• Immunodominant Epitopes
• Lipids
• Liposomes
• MUC1 protein, human
• Mucin-1
• Surface-Active Agents

Topics

• Cancer Vaccines (chemistry, immunology)
• Humans
• Immunodominant Epitopes (immunology)
• Lipids (immunology)
• Liposomes
• MCF-7 Cells
• Mucin-1 (immunology)
• Surface-Active Agents