Journal
CHEMMEDCHEM
Volume 12, Issue 17, Pages 1424-1428Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201700387
Keywords
cancer immunotherapy; glycopeptides; MUC1 antitumor vaccine; MUC1 transgenic mouse
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Funding
- Fonds der Chemischen Industrie
- Deutsche Forschungsgemeinschaft [SFB 1066]
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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 wildtype 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.
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