@article{7c6b67acb9d44452ad0a56ed36e19c7d,
title = "Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma",
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. Posey and colleagues developed a CAR T cell therapy to break immune tolerance to solid tumors by targeting an aberrantly glycosylated, cancer-specific glycoprotein in multiple cancer histotypes and demonstrated efficacy and safety in tumors as diverse as leukemia and pancreatic cancer.",
author = "Posey, {Avery D.} and Schwab, {Robert D.} and Boesteanu, {Alina C.} and Catharina Steentoft and Ulla Mandel and Boris Engels and Stone, {Jennifer D.} and Madsen, {Thomas D.} and Karin Schreiber and Haines, {Kathleen M.} and Cogdill, {Alexandria P.} and Chen, {Taylor J.} and Decheng Song and John Scholler and Kranz, {David M.} and Feldman, {Michael D.} and Regina Young and Brian Keith and Hans Schreiber and Henrik Clausen and Johnson, {Laura A.} and June, {Carl H.}",
note = "Funding Information: We are grateful for advice from Michael Milone and Robert Vonderheide, the Perelman School of Medicine Stem Cell & Xenograft Core, the Human Immunology Core, the Cancer Histology Core, and for staff in the animal facility for assistance with experiments. Supported in part by a grant from Novartis and National Institutes of Health (5R01CA120409, C.H.J.; 5R01CA037156, H.S. and H.C.; and DP2 CA174502, L.A.J.), The Danish Research Councils (DFF – 4004-00397B, C.S.), and The Danish National Research Foundation (DNRF107, H.C.). A.D.P. and C.H.J. are members of the Parker Institute for Cancer Immunotherapy, which supported the University of Pennsylvania Cancer Immunotherapy Program. The University of Copenhagen has patented the 5E5 antibody and antigen epitope. The University of Chicago has filed a patent on the 5E5 CAR and an invention disclosure has been filed on these studies. The University of Pennsylvania has entered into a strategic alliance with Novartis for the development of chimeric antigen receptors. This arrangement is managed in accordance with the University of Pennsylvania{\textquoteright}s Conflict of Interest Policy. The authors are in compliance with this policy. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = jun,
day = "21",
doi = "10.1016/j.immuni.2016.05.014",
language = "English (US)",
volume = "44",
pages = "1444--1454",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "6",
}