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Immunity. 2016 Jun 21;44(6):1444-54. doi: 10.1016/j.immuni.2016.05.014.

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

Author information

1
Center for Cellular Immunotherapies, Abramson Cancer Center and the Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: aposey@mail.med.upenn.edu.
2
Center for Cellular Immunotherapies, Abramson Cancer Center and the Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3
Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark.
4
Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
5
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
6
Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
7
Center for Cellular Immunotherapies, Abramson Cancer Center and the Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
8
Center for Cellular Immunotherapies, Abramson Cancer Center and the Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: cjune@exchange.upenn.edu.

Abstract

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.

PMID:
27332733
PMCID:
PMC5358667
DOI:
10.1016/j.immuni.2016.05.014
[Indexed for MEDLINE]
Free PMC Article

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