Chemoenzymatic Tagging of Tn/TF/STF Antigens in Living Systems

Area of Science:

• Biochemistry
• Glycobiology
• Cancer Biology

Background:

• Truncated mucin-type O-glycans, including Tn-associated antigens, are recognized cancer biomarkers.
• Current antibodies targeting these antigens often lack high affinity or are susceptible to antigen escape.
• Developing effective strategies for targeting these aberrant glycan structures is crucial for cancer therapy.

Purpose of the Study:

• To develop a robust chemoenzymatic strategy for the global labeling of Tn, Thomsen-Friedenreich (TF), and STF antigens in human whole blood.
• To enable efficient and selective targeting of these aberrant cancer biomarkers.

Main Methods:

• Utilized the O-glycan sialyltransferase ST6GalNAc1 for enzymatic labeling.
• Transferred a sialic acid-functionalized adaptor molecule to the GalNAc residue of target antigens.
• Applied the strategy to human whole blood samples for Tn, TF, and STF antigen labeling.

Main Results:

• Achieved high efficiency and selectivity in the global labeling of Tn, TF, and STF antigens.
• Demonstrated successful adaptor functionalization of the target glycan structures.
• Established a tagging system for subsequent targeting strategies.

Conclusions:

• The developed chemoenzymatic strategy provides a robust method for labeling cancer-associated truncated O-glycans.
• Adaptor-functionalized antigens can be effectively targeted by customized strategies, including chimeric antigen receptor T-Cells (CAR-T).
• This tagging system holds significant potential for advancing cancer diagnostics and therapeutic targeting.