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Due to the aberrant glycosylation of MUC1 on tumor cells, tumor-associated MUC1 (tMUC1) has a shortened O-glycan attached on the peptide backbone, distinguishing it from its counterpart on normal cells. Preclinical evaluation of tMUC1-based vaccine candidates typically involved the immunization of mice that are tumor-free. However, tumor development is often associated with immune suppression. To better mimic clinical conditions encountered in cancer treatment, a breast cancer mouse model was built by crossing mouse mammary tumor virus (MMTV)-polyoma middle T (PyMT) mice with human MUC1 transgenic (MUC1.Tg) mice. The resulting female double-transgenic mice (MUC1\/MMTV) spontaneously develop palpable breast cancer from 6 weeks of age. A promising vaccine candidate composed of a short 9-amino-acid Thomsen-nouveau (Tn) antigen containing tMUC1 glycopeptide conjugated with bacteriophage Q\u03b2 was evaluated in MUC1\/MMTV mice. The vaccine was found to be immunogenic and capable of inducing high levels of anti-tMUC1 IgG antibody responses. The antibodies were selective toward both the glycan and the peptide sequence of tMUC1, as deciphered from a glycopeptide microarray study. Furthermore, the induced antibodies bound tumor cells in a MUC1-dependent manner and could kill a range of tumor cells via complement-dependent cytotoxicity. Vaccination with a Q\u03b2-tMUC1 conjugate significantly prolonged the survival of MUC1\/MMTV mice, with 83% of treated MUC1\/MMTV mice outliving the control group. The Q\u03b2-tMUC1 vaccine exhibited promising results in an aggressive and rapidly growing spontaneous tumor model, laying the groundwork for its clinical translation to human patients.<\/jats:p>","DOI":"10.1021\/acschembio.6c00640","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:37:54Z","timestamp":1788453474000},"page":"2504-2513","source":"Crossref","is-referenced-by-count":0,"title":["Effective Tumor Protection by a Tumor-Associated Mucin-1 Glycopeptide-Based Conjugate Vaccine in a Spontaneous Mouse Breast Cancer Model"],"prefix":"10.1021","volume":"21","author":[{"given":"Shivangi","family":"Chugh","sequence":"first","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]},{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8639-4105","authenticated-orcid":true,"given":"Sherif","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]},{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]},{"name":"Benha University , , , ,","place":["Benha, Qaliobiya, Egypt, 13518"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athar","family":"Nakisa","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]},{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Behren","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, 901 87"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, 901 87"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrika","family":"Westerlind","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, 901 87"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6468-5526","authenticated-orcid":true,"given":"Xuefei","family":"Huang","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]},{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]},{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"2026101511062593400_cit1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-025-02305-x","article-title":"Advances in cancer immunotherapy: historical perspectives, current developments, and future directions","volume":"24","author":"Zhang","year":"2025","journal-title":"Mol. 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