Stergiou Natascha, Glaffig Markus, Jonuleit Helmut, Schmitt Edgar, Kunz Horst
Johannes Gutenberg University Mainz, University Medical Center - Institute of Immunology, Langenbeckstraße 1, Building 708, 55131, Mainz, Germany.
Johannes Gutenberg University Mainz, Institute of Organic Chemistry, Duesbergweg 10-14, 55128, Mainz, Germany.
ChemMedChem. 2017 Sep 7;12(17):1424-1428. doi: 10.1002/cmdc.201700387. Epub 2017 Aug 7.
Breaking tolerance is crucial for effective tumor immunotherapy. We showed that vaccines containing tumor-associated human MUC1 glycopeptides induce strong humoral antitumor responses in mice. The question remained whether such vaccines work in humans, in systems where huMUC1 is a self-antigen. To clarify the question, mice transgenic in expressing huMUC1, mimicking the self-tolerant environment, and wild-type mice were vaccinated with a synthetic vaccine. This vaccine comprised STn and Tn antigens bound to a MUC1 tandem repeat peptide coupled to tetanus toxoid. The vaccine induced strong immune responses in wild-type and huMUC1-transgenic mice without auto-aggressive side effects. All antisera exhibited almost equivalent binding to human breast tumor cells. Similar increases of activated B-, CD4 T-, and dendritic cells was found in the lymph nodes. The results demonstrate that tumor-associated huMUC1 glycopeptides coupled to tetanus toxoid are promising antitumor vaccines.
打破耐受性对于有效的肿瘤免疫治疗至关重要。我们发现，含有肿瘤相关人MUC1糖肽的疫苗可在小鼠体内诱导强烈的体液抗肿瘤反应。问题仍然存在，即在人源MUC1为自身抗原的系统中，此类疫苗在人体中是否有效。为了阐明这个问题，我们用一种合成疫苗对表达人源MUC1的转基因小鼠（模拟自身耐受环境）和野生型小鼠进行了接种。这种疫苗包含与破伤风类毒素偶联的MUC1串联重复肽结合的STn和Tn抗原。该疫苗在野生型和人源MUC1转基因小鼠中诱导了强烈的免疫反应，且无自身攻击副作用。所有抗血清与人乳腺肿瘤细胞的结合几乎相当。在淋巴结中发现活化的B细胞、CD4 T细胞和树突状细胞有类似的增加。结果表明，与破伤风类毒素偶联的肿瘤相关人源MUC1糖肽是很有前景的抗肿瘤疫苗。
