A lectin-directed antibody-recruiting molecule against Tn antigen for cancer immunotherapy.

Authors

Bingyu Yan, Haofei Hong, Huiting Li, Jiaxin Peng, Wenxian Cao, Zhimeng Wu

Published in

RSC advances. Oct 16, 2026. Epub Oct 16, 2026.

Abstract

The Tn antigen, an abnormally glycosylated structure on the cell surface, is a key target for cancer immunotherapy. However, the intrinsically weak immunogenicity of glycans and the resulting complex immune tolerance constitute the primary challenges in the clinical translation of Tn-targeted immunotherapies. Native human macrophage galactose lectin (MGL) exhibits a strong binding preference for Tn antigen. Here, we report a Tn-targeting, bifunctional antibody-like molecule ZZ-MGL comprised of an antibody-recruiting domain and a lectin domain. It was demonstrated that ZZ-MGL can target the Tn antigen with high avidity while potently recruiting circulating IgGs in situ. Furthermore, ZZ-MGL could effectively enhance anti-tumor immune responses, by triggering Fc-mediated effector pathways, ultimately translating into significant tumor growth inhibition in a colorectal cancer xenograft mouse model. This chimera platform can potentially be adapted to target other tumor-associated carbohydrate antigens by simply substituting with suitable lectins, highlighting its wide application in cancer immunotherapy.

PMID:
42891405
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.

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