Fucosylation enhances CAR T-cell bone marrow infiltration efficiency
Although chimeric antigen receptor (CAR) T-cell therapy has the potential to revolutionize the way we treat cancer, many challenges remain, not the least of which is cellular infiltration efficacy. A recent paper by Mondal et al (2019) has demonstrated that ex vivo fucosylation enhances the efficiency of CAR T-cell infiltration into bone marrow by 10 fold. Specifically, Fucosyltransferase 6/7-mediated fucosylation of cell surface type 2 sialylLacNAc drives the formation of sialyl Lewis X (sLeX), which is normally decreased on CAR T-cells as a consequence of cell culture expansion. Stable sLeX displayed on the cell membrane allows for enhanced binding to the endothelial lectin E-Selectin. This ligand-receptor interaction is crucial for the tethering and rolling of CAR T-cells in the vasculature. Finally, this paper underscores the fact that glycans represent a crucial yet underrated target for enhancing cell-based therapeutic intervention.