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)