TLRs (Toll-like receptors) are a family of innate immune receptors that induce protective immune responses against infections. Single-stranded viral RNA and bacterial DNA containing unmethylated CpG motifs are the ligands for TLR7 and TLR8 and 9 respectively. We have carried out extensive structure–activity relationship studies of DNA- and RNA-based compounds to elucidate the impact of nucleotide motifs and structures on these TLR-mediated immune responses. These studies have led us to design novel DNA- and RNA-based compounds, which act as potent agonists of TLR9 and TLR7 and 8 respectively. These novel synthetic agonists produce different immune response profiles depending on the structures and nucleotide motifs present in them. The ability to modulate TLR-mediated immune responses with these novel DNA- and RNA-based agonists in a desired fashion may allow targeting a broad range of diseases, including cancers, asthma, allergies and infections, alone or in combination with other therapeutic agents, and their use as adjuvants with vaccines. IMO-2055, our first lead candidate, is a TLR9 agonist that is currently in clinical evaluation in oncology patients. A second candidate, IMO-2125, is also a TLR9 agonist that has been shown to induce high and sustained levels of IFN (interferon) in non-human primates and is being evaluated in HepC-infected human subjects.
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December 2007
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Conference Article|
November 23 2007
Synthetic agonists of Toll-like receptors 7, 8 and 9
S. Agrawal;
S. Agrawal
1
1Idera Pharmaceuticals, 167 Sidney Street, Cambridge, MA 02139, U.S.A.
1To whom correspondence should addressed (email sagrawal@iderapharma.com).
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E.R. Kandimalla
E.R. Kandimalla
1Idera Pharmaceuticals, 167 Sidney Street, Cambridge, MA 02139, U.S.A.
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Publisher: Portland Press Ltd
Received:
August 29 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (6): 1461–1467.
Article history
Received:
August 29 2007
Citation
S. Agrawal, E.R. Kandimalla; Synthetic agonists of Toll-like receptors 7, 8 and 9. Biochem Soc Trans 1 December 2007; 35 (6): 1461–1467. doi: https://doi.org/10.1042/BST0351461
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