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Degrading sialoglycans delays tumour growth

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Cell surface sialoglycans suppress immune activation and are upregulated in malignancy, representing a potential target for cancer immune therapy. Building on previous work, Gray et al. optimize a targeted degradation strategy, in which a sialic acid-cleaving enzyme (sialidase) is fused to a HER2-targeting antibody, trastuzumab, to catalytically degrade sialoglycans in a tumour-specific manner. In mouse breast cancer models, the antibody–sialidase conjugate delayed tumour growth and enhanced immune cell infiltration, prolonging survival. These effects were dependent on Siglec-E checkpoint receptor expression on tumour-infiltrating myeloid cells.

Nature Reviews Drug Discovery 19, 672 (2020)

References

  1. 1.

    Gray, M. A. et al. Targeted glycan degradation potentiates the anticancer immune response in vivo. Nat. Chem. Biol. https://doi.org/10.1038/s41589-020-0622-x (2020)

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