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Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma

2016; Cell Press; Volume: 44; Issue: 6 Linguagem: Inglês

10.1016/j.immuni.2016.05.014

1097-4180

Avery D. Posey, Robert D. Schwab, Alina C. Boesteanu, Catharina Steentoft, Ulla Mandel, Boris Engels, Jennifer D. Stone, Thomas D. Madsen, Karin Schreiber, Kathleen M. Haines, Alexandria P. Cogdill, Taylor J Chen, Decheng Song, John Scholler, David M. Kranz, Michael D. Feldman, Regina M. Young, Brian Keith, Hans Schreiber, Henrik Clausen, Laura A. Johnson, Carl H. June,

Nanowire Synthesis and Applications

Genetically modified T cells expressing chimeric antigen receptors (CARs) demonstrate robust responses against lineage restricted, non-essential targets in hematologic cancers. However, in solid tumors, the full potential of CAR T cell therapy is limited by the availability of cell surface antigens with sufficient cancer-specific expression. The majority of CAR targets have been normal self-antigens on dispensable hematopoietic tissues or overexpressed shared antigens. Here, we established that abnormal self-antigens can serve as targets for tumor rejection. We developed a CAR that recognized cancer-associated Tn glycoform of MUC1, a neoantigen expressed in a variety of cancers. Anti-Tn-MUC1 CAR T cells demonstrated target-specific cytotoxicity and successfully controlled tumor growth in xenograft models of T cell leukemia and pancreatic cancer. These findings demonstrate the therapeutic efficacy of CAR T cells directed against Tn-MUC1 and present aberrantly glycosylated antigens as a novel class of targets for tumor therapy with engineered T cells.