Targeting glycans for CAR therapy: The advent of sweet CARs

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.

Keywords: CAR T cell therapy; cancer glycobiology; glycan; glycoprotein; solid tumor; tumor microenvironment.