ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
One-Step Glycoengineering of NK Cells With High-Affinity Siglec Ligands for Cancer Immunotherapy.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Biomaterial engineering of the tumor glycocalyx for cancer immunotherapy.Materials today. Bio · 2026Review
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9 authors.
Funding
Abstract
Siglecs, a family of sialic acid (Sia)-binding immunomodulatory receptors selectively expressed on immune cells, are promising immunotherapeutic targets. While synthetic Sia derivatives can manipulate the Sia-Siglec axis with high affinity, their therapeutic application has been hampered by the poor substrate tolerance of wild-type CMP-sialic acid synthase (CSS) for sterically demanding analogs. Here, we report a structure-guided engineering strategy to evolve Neisseria meningitidis CMP-Sia synthetase (NmCSS) for enhanced activity with bulky substrates. Coupling this optimized NmCSS variant with a sialyltransferase enabled a scalable "one-pot two-enzyme" (OPTE) synthesis of diverse sialoside analogs. Screening this library on glycan microarrays revealed novel high-affinity ligands with selective Siglec binding profiles. Leveraging the OPTE system, we achieved single-step glycoengineering of natural killer (NK)-92MI cells with tailored Siglec-2 or Siglec-3 ligands, which exhibited potent cytotoxicity against B-cell lymphoma (Siglec-2
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