{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:45:14Z","timestamp":1789501514054,"version":"build-2803163510"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Antibody-derived chimeric antigen receptor (CAR) T cell therapy has achieved gratifying breakthrough in hematologic malignancies but has shown limited success in solid tumor immunotherapy. Monoclonal antibody, TAB004, specifically recognizes the aberrantly glycosylated tumor form of MUC1 (tMUC1) in all subtypes of breast cancer including 95% of triple-negative breast cancer (TNBC) while sparing recognition of normal tissue MUC1. We transduced human T cells with MUC28z, a chimeric antigen receptor comprising of the scFv of TAB004 coupled to CD28 and CD3\u03b6. MUC28z was well-expressed on the surface of engineered activated human T cells. MUC28z CAR T cells demonstrated significant target-specific cytotoxicity against a panel of human TNBC cells. Upon recognition of tMUC1 on TNBC cells, MUC28z CAR T cells increased production of Granzyme B, IFN-\u03b3 and other Th1 type cytokines and chemokines. A single dose of MUC28z CAR T cells significantly reduced TNBC tumor growth in a xenograft model. Thus, MUC28z CAR T cells have high therapeutic potential against tMUC1-positive TNBC tumors with minimal damage to normal breast epithelial cells.<\/jats:p>","DOI":"10.3389\/fimmu.2019.01149","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T12:53:20Z","timestamp":1558702400000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":175,"title":["CAR T Cells Targeting the Tumor MUC1 Glycoprotein Reduce Triple-Negative Breast Cancer Growth"],"prefix":"10.3389","volume":"10","author":[{"given":"Ru","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboubeh","family":"Yazdanifar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lopamudra Das","family":"Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynsey M.","family":"Whilding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artemis","family":"Gavrill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Maher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinku","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,5,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1056\/NEJMra1001389","article-title":"Triple-negative breast cancer","volume":"363","author":"Foulkes","year":"2010","journal-title":"N Engl J Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1038\/nrclinonc.2016.36","article-title":"Driving CAR T-cells forward","volume":"13","author":"Jackson","year":"2016","journal-title":"Nat Rev Clin Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s10549-007-9756-8","article-title":"Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients","volume":"111","author":"Tan","year":"2008","journal-title":"Breast Cancer Res Treat."},{"key":"B4","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1158\/2159-8290.CD-12-0548","article-title":"The basic principles of chimeric antigen receptor design","volume":"3","author":"Sadelain","year":"2013","journal-title":"Cancer Discov."},{"key":"B5","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.coi.2016.06.004","article-title":"Chimeric antigen receptors: driving immunology towards synthetic biology","volume":"41","author":"Sadelain","year":"2016","journal-title":"Curr Opin Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e1273302","DOI":"10.1080\/2162402X.2016.1273302","article-title":"CAR T-cell intrinsic PD-1 checkpoint blockade: a two-in-one approach for solid tumor immunotherapy","volume":"6","author":"Chen","year":"2017","journal-title":"Oncoimmunology."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e360","DOI":"10.14694\/EdBook_AM.2015.35.e360","article-title":"CD19 CAR therapy for acute lymphoblastic leukemia","volume":"2015","author":"Sadelain","year":"2015","journal-title":"Am Soc Clin Oncol Educ Book."},{"key":"B8","doi-asserted-by":"publisher","first-page":"4901","DOI":"10.4049\/jimmunol.180.7.4901","article-title":"Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor","volume":"180","author":"Wilkie","year":"2008","journal-title":"J Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1016\/j.immuni.2016.05.014","article-title":"Engineered CAR T cells targeting the cancer-associated Tn-glycoform of the membrane mucin MUC1 control adenocarcinoma","volume":"44","author":"Posey","year":"2016","journal-title":"Immunity."},{"key":"B10","first-page":"95","article-title":"Emerging immunotherapeutics in adenocarcinomas: a focus on CAR-T cells","volume":"17","author":"Yazdanifar","year":"2016","journal-title":"Curr Trends Immunol."},{"key":"B11","doi-asserted-by":"crossref","first-page":"12820","DOI":"10.1016\/S0021-9258(18)37632-4","article-title":"A highly immunogenic region of a human polymorphic epithelial mucin expressed by carcinomas is made up of tandem repeats","volume":"263","author":"Gendler","year":"1988","journal-title":"J Biol Chem."},{"key":"B12","doi-asserted-by":"crossref","first-page":"15286","DOI":"10.1016\/S0021-9258(18)77254-2","article-title":"Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin","volume":"265","author":"Gendler","year":"1990","journal-title":"J Biol Chem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"18165","DOI":"10.1074\/jbc.274.26.18165","article-title":"High density O-glycosylation on tandem repeat peptide from secretory MUC1 of T47D breast cancer cells","volume":"274","author":"Muller","year":"1999","journal-title":"J Biol Chem."},{"key":"B14","doi-asserted-by":"crossref","first-page":"21364","DOI":"10.1016\/S0021-9258(19)36932-7","article-title":"The epithelial sialomucin, episialin, is sialylated during recycling","volume":"268","author":"Litvinov","year":"1993","journal-title":"J Biol Chem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1111\/j.1432-1033.1995.607_2.x","article-title":"Mechanisms underlying aberrant glycosylation of MUC1 mucin in breast cancer cells","volume":"233","author":"Brockhausen","year":"1995","journal-title":"Eur J Biochem."},{"key":"B16","doi-asserted-by":"publisher","first-page":"11007","DOI":"10.1074\/jbc.M006523200","article-title":"The relative activities of the C2GnT1 and ST3Gal-I glycosyltransferases determine O-glycan structure and expression of a tumor-associated epitope on MUC1","volume":"276","author":"Dalziel","year":"2001","journal-title":"J Biol Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1038\/modpathol.3800445","article-title":"Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer","volume":"18","author":"Rakha","year":"2005","journal-title":"Modern Pathol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1002\/jso.23316","article-title":"The use of a novel MUC1 antibody to identify cancer stem cells and circulating MUC1 in mice and patients with pancreatic cancer","volume":"107","author":"Curry","year":"2013","journal-title":"J Surg Oncol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"536","DOI":"10.18632\/genesandcancer.134","article-title":"A tumor specific antibody to aid breast cancer screening in women with dense breast tissue","volume":"8","author":"Roy","year":"2017","journal-title":"Genes Cancer."},{"key":"B20","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.tranon.2016.05.001","article-title":"Antibody-guided in vivo imaging for early detection of mammary gland tumors","volume":"9","author":"Moore","year":"2016","journal-title":"Transl Oncol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.ymthe.2017.09.018","article-title":"Targeting of aberrant alphavbeta6 integrin expression in solid tumors using chimeric antigen receptor-engineered T cells","volume":"25","author":"Whilding","year":"2017","journal-title":"Mol Ther."},{"key":"B22","doi-asserted-by":"publisher","first-page":"261ra151","DOI":"10.1126\/scitranslmed.3010162","article-title":"Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity","volume":"6","author":"Adusumilli","year":"2014","journal-title":"Sci Transl Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"11428","DOI":"10.1158\/0008-5472.CAN-07-1141","article-title":"Sustained antigen-specific antitumor recall response mediated by gene-modified CD4+ T helper-1 and CD8+ T cells","volume":"67","author":"Moeller","year":"2007","journal-title":"Cancer Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1200\/JCO.2014.56.2025","article-title":"Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor","volume":"33","author":"Kochenderfer","year":"2015","journal-title":"J Clin Oncol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"303ra139","DOI":"10.1126\/scitranslmed.aac5415","article-title":"Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia","volume":"7","author":"Porter","year":"2015","journal-title":"Sci Transl Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"5608","DOI":"10.1038\/onc.2015.516","article-title":"A novel association of neuropilin-1 and MUC1 in pancreatic ductal adenocarcinoma: role in induction of VEGF signaling and angiogenesis","volume":"35","author":"Zhou","year":"2016","journal-title":"Oncogene."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3370","DOI":"10.1002\/eji.200425587","article-title":"Down-regulation of CXCR4 expression on human CD8+ T cells during peripheral differentiation","volume":"34","author":"Kobayashi","year":"2004","journal-title":"Eur J Immunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/1465-9921-6-70","article-title":"The beta2 integrin CD11c distinguishes a subset of cytotoxic pulmonary T cells with potent antiviral effects in vitro and in vivo","volume":"6","author":"Beyer","year":"2005","journal-title":"Respir Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"8924","DOI":"10.1038\/srep08924","article-title":"Wilms' tumor 1 (WT1) expression and prognosis in solid cancer patients: a systematic review and meta-analysis","volume":"5","author":"Qi","year":"2015","journal-title":"Sci Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/onc.2012.158","article-title":"MUC1-C oncoprotein as a target in breast cancer: activation of signaling pathways and therapeutic approaches","volume":"32","author":"Kufe","year":"2013","journal-title":"Oncogene."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1007\/s10875-012-9689-9","article-title":"Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling","volume":"32","author":"Wilkie","year":"2012","journal-title":"J Clin Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1016\/j.immuni.2016.10.015","article-title":"Distinguishing truncated and normal MUC1 glycoform targeting from Tn-MUC1-specific CAR T cells: specificity is the key to safety","volume":"45","author":"Posey","year":"2016","journal-title":"Immunity."},{"key":"B33","doi-asserted-by":"publisher","first-page":"735","DOI":"10.4161\/onci.20823","article-title":"PD-1 and BTLA and CD8(+) T-cell \u201cexhaustion\u201d in cancer: \u201cexercising\u201d an alternative viewpoint","volume":"1","author":"Haymaker","year":"2012","journal-title":"Oncoimmunology."},{"key":"B34","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1182\/blood-2006-12-062422","article-title":"Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells","volume":"110","author":"Goldberg","year":"2007","journal-title":"Blood."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1158\/2159-8290.CD-18-0442","article-title":"Tumor antigen escape from CAR T-cell therapy","volume":"8","author":"Majzner","year":"2018","journal-title":"Cancer Discov."},{"key":"B36","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat Rev Cancer."},{"key":"B37","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.coi.2015.02.003","article-title":"The interplay of effector and regulatory T cells in cancer","volume":"33","author":"Roychoudhuri","year":"2015","journal-title":"Curr Opin Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.smim.2016.01.002","article-title":"Enhancing T cell therapy by overcoming the immunosuppressive tumor microenvironment","volume":"28","author":"Arina","year":"2016","journal-title":"Semin Immunol."}],"updated-by":[{"DOI":"10.3389\/fimmu.2020.628776","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000}}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2019.01149\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T15:57:19Z","timestamp":1663516639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2019.01149\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,24]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2019.01149"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2019.01149","relation":{"corrigendum":[{"id-type":"doi","id":"10.3389\/fimmu.2020.628776","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,24]]},"article-number":"1149"}}