Glaffig Markus, Stergiou Natascha, Schmitt Edgar, Kunz Horst
Johannes Gutenberg University Mainz, Institute of Organic Chemistry, Duesbergweg 10-14, 55128, Mainz, Germany.
Johannes Gutenberg University Mainz, University Medical Center, Institute of Immunology, Langenbeckstrasse 1, Geb. 708, 55101, Mainz, Germany.
ChemMedChem. 2017 May 22;12(10):722-727. doi: 10.1002/cmdc.201700254. Epub 2017 May 5.
Fully synthetic MUC1 glycopeptide antitumor vaccines have a precisely specified structure and induce a targeted immune response without suppression of the immune response when using an immunogenic carrier protein. However, tumor-associated aberrantly glycosylated MUC1 glycopeptides are endogenous structures, "self-antigens", that exhibit only low immunogenicity. To overcome this obstacle, a fully synthetic MUC1 glycopeptide antitumor vaccine was combined with poly(inosinic acid:cytidylic acid), poly(I:C), as a structurally defined Toll-like receptor 3 (TLR3)-activating adjuvant. This vaccine preparation elicited extraordinary titers of IgG antibodies which strongly bound human breast cancer cells expressing tumor-associated MUC1. Beside the humoral response, the poly(I:C) glycopeptide vaccine induced a pro-inflammatory environment, very important to overcome the immune-suppressive mechanisms, and elicited a strong cellular immune response crucial for tumor elimination.
完全合成的MUC1糖肽抗肿瘤疫苗具有精确指定的结构，并且在使用免疫原性载体蛋白时可诱导靶向免疫反应而不会抑制免疫反应。然而，肿瘤相关的异常糖基化MUC1糖肽是内源性结构，即“自身抗原”，其仅表现出低免疫原性。为了克服这一障碍，将完全合成的MUC1糖肽抗肿瘤疫苗与聚（肌苷酸：胞苷酸），即聚（I：C）结合，作为结构明确的Toll样受体3（TLR3）激活佐剂。这种疫苗制剂引发了高滴度的IgG抗体，这些抗体与表达肿瘤相关MUC1的人乳腺癌细胞强烈结合。除了体液反应外，聚（I：C）糖肽疫苗还诱导了促炎环境，这对于克服免疫抑制机制非常重要，并引发了对肿瘤消除至关重要的强烈细胞免疫反应。
