Targeting glycans for CAR therapy: The advent of sweet CARs

Zoe Raglow, Mary Kathryn McKenna, Challice L. Bonifant, Wenjing Wang, Marina Pasca di Magliano, Johannes Stadlmann, Josef M. Penninger, Richard D. Cummings, Malcolm K. Brenner, David M. Markovitz

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Chimeric antigen receptor (CAR) T cell therapy has created a paradigm shift in the treatment of hematologic malignancies but has not been as effective toward solid tumors. For such tumors, the primary obstacles facing CAR T cells are scarcity of tumor-specific antigens and the hostile and complex tumor microenvironment. Glycosylation, the process by which sugars are post-translationally added to proteins or lipids, is profoundly dysregulated in cancer. Abnormally glycosylated glycoproteins expressed on cancer cells offer unique targets for CAR T therapy as they are specific to tumor cells. Tumor stromal cells also express abnormal glycoproteins and thus also have the potential to be targeted by glycan-binding CAR T cells. This review will discuss the state of CAR T cells in the therapy of solid tumors, the cancer glycoproteome and its potential for use as a therapeutic target, and the landscape and future of glycan-binding CAR T cell therapy.

Original languageEnglish (US)
Pages (from-to)2881-2890
Number of pages10
JournalMolecular Therapy
Volume30
Issue number9
DOIs
StatePublished - Sep 7 2022

Keywords

  • CAR T cell therapy
  • cancer glycobiology
  • glycan
  • glycoprotein
  • solid tumor
  • tumor microenvironment

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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