Natural killer cells are able to directly lyse tumor cells, thereby participating in the immune surveillance against cancer. Unfortunately, many cancer cells use immune evasion strategies to avoid their eradication by the immune system. A prominent escape strategy of malignant cells is to camouflage themselves with Siglec-7 ligands, thereby recruiting the inhibitory receptor Siglec-7 expressed on the NK cell surface which subsequently inhibits NK-cell-mediated lysis. Here we describe the synthesis and evaluation of the first, high-affinity low molecular weight Siglec-7 ligands to interfere with cancer cell immune evasion. The compounds are Sialic acid derivatives and bind with low micromolar Kd values to Siglec-7. They display up to a 5000-fold enhanced affinity over the unmodified sialic acid scaffold αMe Neu5Ac, the smallest known natural Siglec-7 ligand. Our results provide a novel immuno-oncology strategy employing natural immunity in the fight against cancers, in particular blocking Siglec-7 with low molecular weight compounds.
Pharmacology, Toxicology and Pharmaceutical Science
6
10%
Biochemistry, Genetics and Molecular Biology
6
10%
Agricultural and Biological Sciences
6
10%
Immunology and Microbiology
5
8%
Other
4
6%
Unknown
19
30%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 February 2017.
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#20,400,885
of 22,950,943 outputs
Outputs from Journal of Medicinal Chemistry
#21,625
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Outputs of similar age
#353,486
of 417,732 outputs
Outputs of similar age from Journal of Medicinal Chemistry
#121
of 125 outputs
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