Center for Medical Ethics and Health Policy Staff Publications
Publication Date
9-7-2022
Journal
Molecular Therapy
DOI
10.1016/j.ymthe.2022.07.006
PMID
35821636
PMCID
PMC9481985
PubMedCentral® Posted Date
9-7-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Glycoproteins, Humans, Immunotherapy, Adoptive, Neoplasms, Polysaccharides, Receptors, Antigen, T-Cell, Tumor Microenvironment
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.