MUC1 Specific Immune Responses Enhanced by Coadministration of Liposomal DDA/MPLA and Lipoglycopeptide.

MUC1 Specific Immune Responses Enhanced by Coadministration of Liposomal DDA/MPLA and Lipoglycopeptide.
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脂质体 DDA/MPLA 和脂糖肽共同给药增强 MUC1 特异性免疫反应

DOI:
10.3389/fchem.2022.814880
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发表时间:
2022
影响因子:
5.5
通讯作者:
Guo J
Guo J
中科院分区:
化学3区
文献类型:
--
作者:
Du JJ;Zhou SH;Cheng ZR;Xu WB;Zhang RY;Wang LS;Guo J

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Mucin 1 (MUC1), a well-known tumor-associated antigen and attractive target for tumor immunotherapy, is overexpressed in most human epithelial adenomas with aberrant glycosylation. However, its low immunogenicity impedes the development of MUC1-targeted antitumor vaccines. In this study, we investigated three liposomal adjuvant systems containing toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) and auxiliary lipids of different charges: cationic lipid dimethyldioctadecylammonium (DDA), neutral lipid distearoylglycerophosphocholine (DSPC) or anionic lipid dioleoylphosphatidylglycerol (DOPG), respectively. ELISA assay evidenced that the positively charged DDA/MPLA liposomes are potent immune activators, which induced remarkable levels of anti-MUC1 antibodies and exhibited robust Th1-biased immune responses. Importantly, the antibodies induced by DDA/MPLA liposomes efficiently recognized and killed MUC1-positive tumor cells through complement-mediated cytotoxicity. In addition, antibody titers in mice immunized with P2-MUC1 vaccine were significantly higher than those from mice immunized with P1-MUC1 or MUC1 vaccine, which indicated that the lipid conjugated on MUC1 antigen also played important role for immunomodulation. This study suggested that the liposomal DDA/MPLA with lipid-MUC1 is a promising antitumor vaccine, which can be used for the immunotherapy of various epithelial carcinomas represented by breast cancer.
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