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

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 Young, Brian Keith, Hans Schreiber, Henrik Clausen & 2 others Laura A. Johnson, Carl H. June

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1444-1454
Number of pages11
JournalImmunity
Volume44
Issue number6
DOIs
StatePublished - Jun 21 2016

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Mucins
T-Cell Antigen Receptor
Adenocarcinoma
Membranes
Antigen Receptors
Neoplasms
Autoantigens
Cell- and Tissue-Based Therapy
Pancreatic Neoplasms
T-Lymphocytes
T-Cell Leukemia
Antigens
Immune Tolerance
Surface Antigens
Heterografts
Glycoproteins
Leukemia
Safety

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Posey, A. D., Schwab, R. D., Boesteanu, A. C., Steentoft, C., Mandel, U., Engels, B., ... June, C. H. (2016). Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma. Immunity, 44(6), 1444-1454. https://doi.org/10.1016/j.immuni.2016.05.014

Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma. / Posey, Avery D.; Schwab, Robert D.; Boesteanu, Alina C.; Steentoft, Catharina; Mandel, Ulla; Engels, Boris; Stone, Jennifer D.; Madsen, Thomas D.; Schreiber, Karin; Haines, Kathleen M.; Cogdill, Alexandria P.; Chen, Taylor J.; Song, Decheng; Scholler, John; Kranz, David M; Feldman, Michael D.; Young, Regina; Keith, Brian; Schreiber, Hans; Clausen, Henrik; Johnson, Laura A.; June, Carl H.

In: Immunity, Vol. 44, No. 6, 21.06.2016, p. 1444-1454.

Research output: Contribution to journalArticle

Posey, AD, Schwab, RD, Boesteanu, AC, Steentoft, C, Mandel, U, Engels, B, Stone, JD, Madsen, TD, Schreiber, K, Haines, KM, Cogdill, AP, Chen, TJ, Song, D, Scholler, J, Kranz, DM, Feldman, MD, Young, R, Keith, B, Schreiber, H, Clausen, H, Johnson, LA & June, CH 2016, 'Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma', Immunity, vol. 44, no. 6, pp. 1444-1454. https://doi.org/10.1016/j.immuni.2016.05.014
Posey, Avery D. ; Schwab, Robert D. ; Boesteanu, Alina C. ; Steentoft, Catharina ; Mandel, Ulla ; Engels, Boris ; Stone, Jennifer D. ; Madsen, Thomas D. ; Schreiber, Karin ; Haines, Kathleen M. ; Cogdill, Alexandria P. ; Chen, Taylor J. ; Song, Decheng ; Scholler, John ; Kranz, David M ; Feldman, Michael D. ; Young, Regina ; Keith, Brian ; Schreiber, Hans ; Clausen, Henrik ; Johnson, Laura A. ; June, Carl H. / Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma. In: Immunity. 2016 ; Vol. 44, No. 6. pp. 1444-1454.
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