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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Avery D Posey
  • Robert D Schwab
  • Alina C Boesteanu
  • Catharina Steentoft
  • Boris Engels
  • Jennifer D Stone
  • 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
  • Laura A Johnson
  • Carl H June
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.
Original languageEnglish
Issue number6
Pages (from-to)1444-1454
Number of pages11
Publication statusPublished - 21 Jun 2016

ID: 166270067