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Siglecs as targets for therapy in immune-cell-mediated disease
Open accessAbstract
The sialic acid-binding immunoglobulin-like lectins (siglecs) comprise a family of receptors that are differentially expressed on leukocytes and other immune cells. The restricted expression of several siglecs to one or a few cell types makes them attractive targets for cell-directed therapies. The anti-CD33 (Siglec-3) antibody Gemtuzumab (Mylotarg™) is approved for treatment of acute myeloid leukemia (AML), and antibodies targeting CD22 (Siglec-2) are currently in clinical trials for treatment of B cell non-Hodgkins lymphomas and autoimmune diseases. Because siglecs are endocytic receptors, they are well suited for a ‘Trojan horse’ strategy, whereby therapeutic agents conjugated to an antibody, or multimeric glycan ligand, bind to the siglec and are efficiently carried into the cell. Although the rapid internalization of unmodified siglec antibodies reduces their utility for induction of antibody-dependent cellular cytotoxicity (ADCC) or complement-mediated cytotoxicity (CDC), antibody binding of Siglec-8, Siglec-9, and CD22 have been demonstrated to induce apoptosis of eosinophils, neutrophils, and depletion of B cells, respectively. Here we review the properties of siglecs that make them attractive for cell-targeted therapies.
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Cites
Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis
Kim, S., Takahashi, H., Lin, W.-W., Descargues, P., Grivennikov, S., Kim, Y., Luo, J.-L., & Karin, M. (2009) · Nature · doi:10.1038/nature07623 · Cited by 1,100
Avril, T., Wagner, E. R., Willison, H. J., & Crocker, P. R. (2006) · Infection and Immunity · doi:10.1128/iai.02094-05 · Cited by 133
Cited by
Siglec-mediated regulation of immune cell function in disease
Macauley, M. S., Crocker, P. R., & Paulson, J. C. (2014) · Nature Reviews Immunology · doi:10.1038/nri3737 · Cited by 1,122
Self-citationAlzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta
Griciuc, A., Serrano-Pozo, A., Parrado, A. R., Lesinski, A. N., Asselin, C. N., Mullin, K., Hooli, B., Choi, S. H., Hyman, B. T., & Tanzi, R. E. (2013) · Neuron · doi:10.1016/j.neuron.2013.04.014 · Cited by 1,004
Ricart, A. D. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-0486 · Cited by 332
Siglec-G/10 in self-nonself discrimination of innate and adaptive immunity
Chen, G.-Y., Brown, N. K., Zheng, P., & Liu, Y. (2014) · Glycobiology · doi:10.1093/glycob/cwu068 · Cited by 90
Bax, M., Kuijf, M. L., Heikema, A. P., van Rijs, W., Bruijns, S. C. M., García-Vallejo, J. J., Crocker, P. R., Jacobs, B. C., van Vliet, S. J., & van Kooyk, Y. (2011) · Infection and Immunity · doi:10.1128/iai.00009-11 · Cited by 82
Metadata
- Authors
- O’Reilly, M. K., & Paulson, J. C.
- Venue
- Trends in Pharmacological Sciences
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 30
- Issue
- 5
- Pages
- 240-248
- ISSN
- 0165-6147 (ISSN-L)
- OpenAlex
- W1993160668
- Cited by
- 187
- References
- 2
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- green
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