期刊
IMMUNITY
卷 44, 期 6, 页码 1444-1454出版社
CELL PRESS
DOI: 10.1016/j.immuni.2016.05.014
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资金
- Novartis
- National Institutes of Health [5R01CA120409, 5R01CA037156, DP2 CA174502]
- Danish Research Councils [DFF - 4004-00397B]
- Danish National Research Foundation [DNRF107]
- Parker Institute for Cancer Immunotherapy
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.
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