Dr. Li, Chia-Wei 's publons link picture

Dr. Li, Chia-Wei

Assistant Research Fellow
  • 02-2789-9055 (Lab) (Room No: N147)
  • 02-2652-3912 (Office)
  • 02-2782-9224 (Fax)

Specialty:
  • Cancer immunotherapy
  • Antibody discovery
  • Cancer metastasis

Education and Positions:
  • Ph.D. Rutgers University


Highlight Detail
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Deglycosylation of SLAMF7 in breast cancers enhances phagocytosis

Dr. Li, Chia-Wei
American Journal of Cancer Research, Oct 15, 2022

 

 

 

N-linked glycosylation of proteins is one of the post-translational modifications (PTMs) that shield tumor antigens from immune attack. Signaling lymphocytic activation molecule family 7 (SLAMF7) suppresses cancer cell phagocytosis and is an ideal target under clinical development. PTM of SLAMF7, however, remains less understood. In this study, we investigated the role of N-glycans on SLAMF7 in breast cancer progression. We identified seven N-linked glycosylation motifs on SLAMF7, which are majorly occupied by complex structures. Evolutionally conserved N98 residue is enriched with high mannose and sialylated glycans. Hyperglycosylated SLAMF7 was associated with STT3A expression in breast cancer cells. Inhibition of STT3A by a small molecule inhibitor, N-linked glycosylation inhibitor-1 (NGI-1), reduced glycosylation of SLAMF7, resulting in enhancing antibody affinity and phagocytosis. To provide an on-target effect, we developed an antibody-drug conjugate (ADC) by coupling the anti-SLAMF7 antibody with NGI-1. Deglycosylation of SLAMF7 increases antibody recognition and promotes macrophage engulfment of breast cancer cells. Our work suggests deglycosylation by ADC is a potential strategy to enhance the response of immunotherapeutic agents.