Directing CAR NK Cells via the Metabolic Incorporation of CAR Ligands into Malignant Cell Glycans.

ABSTRACT: The abundance of sialic acid-containing glycans in the glycocalyx of malignant cells enables immune evasion. Here, we leverage the biosynthetic pathways that permit pervasive sialylation to incorporate a chimeric antigen receptor (CAR) ligand into malignant cell glycans, and demonstrate that this increases the susceptibility of malignant cells to the cytolytic activity of CAR-expressing natural killer (NK) cells. Specifically, we applied a C-9-functionalized nonnatural sialic acid [i.e., fluorescein sialic acid (FL-SA)] to modify malignant cell glycans. We confirm the metabolic incorporation of FL-SA into plasma membrane-associated glycans. The preparation of anti-fluorescein CAR NK cells permitted studies demonstrating that treating malignant cells with FL-SA increased susceptibility to C

SUBMITTER: Antillon K 

PROVIDER: S-EPMC10061155 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature