Galectin-3 ligands on CAR-T cell surface glycans (Gal-3 ligands)

Galectin-3 ligands on CAR-T cell surface glycans refer to the specific carbohydrate motifs, such as poly-N-acetyllactosamine (poly-LacNAc) chains, that are present on the glycoproteins of engineered T cells. These glycans serve as the primary binding partners for Galectin-3, a beta-galactoside-binding lectin frequently overexpressed in the tumor microenvironment (TME) by tumor and myeloid cells (Kouo et al., 2015, PMID: 26030227). Upon binding, Galectin-3 facilitates the formation of a multivalent galectin-glycan lattice that cross-links and sequesters essential signaling receptors like the T-cell receptor (TCR) or the Chimeric Antigen Receptor (CAR) itself (Rabinovich et al., 2012, PMID: 22416234). This lattice formation restricts the lateral mobility of surface receptors, leading to reduced CAR-T cell motility, impaired tumor infiltration, and the induction of a dysfunctional or exhausted state (Foster et al., 2023, PMID: 37164956). Therapeutic targeting of this axis involves the use of small-molecule Galectin-3 inhibitors, such as Belapectin or GB1211, or the genetic engineering of CAR-T cells to increase surface sialylation, which masks these ligands and prevents Galectin-3 binding. By disrupting this interaction, researchers aim to enhance the persistence and cytotoxic efficacy of CAR-T cell therapies in challenging solid tumor environments. Monitoring Galectin-3 levels and the glycan signature of infused cells is emerging as a vital strategy for optimizing treatment outcomes in patients with Galectin-3-rich tumors.

Other names

CAR-T cell surface glycansGalectin-3-binding glycansPoly-N-acetyllactosamine chainsGal-3-binding carbohydratesN-acetyllactosamine (LacNAc) motifs

Inhibition of Galectin-3 binding to surface glycans to prevent lattice formation and restore T-cell activity.