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Immunization with a synthetic human MUC1 glycopeptide vaccine against tumor-associated MUC1 breaks tolerance in human MUC1 transgenic mice.

Immunization with a synthetic human MUC1 glycopeptide vaccine against tumor-associated MUC1 breaks tolerance in human MUC1 transgenic mice.
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Kunz H, Stergiou N, Glaffig M, Jonuleit H, Schmitt E,


Kunz H, Stergiou N, Glaffig M, Jonuleit H, Schmitt E, (click to view)

Kunz H, Stergiou N, Glaffig M, Jonuleit H, Schmitt E,

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ChemMedChem 2017 07 04() doi 10.1002/cmdc.201700387

Abstract

Breaking the tolerance is crucial for an effective tumor immunotherapy. We showed that vaccines containing tumor-associated human MUC1 glycopeptides induce strong humoral anti-tumor 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 increase of activated B-, CD4+ T- and dendritic cells was found in the lymphnodes. The results demonstrate that tumor-associated huMUC1 glycopeptides coupled to Tetanus Toxoid are promising antitumor vaccines.

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