What is R848?
R848 (Resiquimod) is an imidazoquinoline compound with potent anti-viral activity. This low molecular weight synthetic molecule activates immune cells via the TLR7/TLR8 MyD88-dependent signaling pathway [1, 2].
What is TLR7 8 agonist?
Small molecule Toll-like receptor (TLR) 7/8 agonists have demonstrated potential as vaccine adjuvants, since they directly activate APCs and can enhance both humoral and cellular immune responses, especially Th1 responses.
Is Resiquimod FDA approved?
Currently, there are three FDA-approved nucleoside analogs and other therapies such as foscarnet and cidofovir used to treat genital herpes. Resiquimod, the latest immune response modifier (IRM), has shown in vivo evidence of efficacy against herpes simplex virus (HSV) type 2.
Why is it called toll like receptors?
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. TLRs received their name from their similarity to the protein coded by the toll gene identified in Drosophila in 1985 by Christiane Nüsslein-Volhard and Eric Wieschaus.
What are the types of agonists?
Types of agonists. Receptors can be activated by either endogenous agonists (such as hormones and neurotransmitters) or exogenous agonists (such as drugs), resulting in a biological response. A physiological agonist is a substance that creates the same bodily responses but does not bind to the same receptor.
Where is TLR7 located?
human X chromosome
This gene is predominantly expressed in lung, placenta, and spleen, and lies in close proximity to another family member, TLR8, on the human X chromosome. TLR7 recognizes single-stranded RNA in endosomes, which is a common feature of viral genomes which are internalised by macrophages and dendritic cells.
How is r848 used to treat pancreatic cancer?
No tumor mass differences were observed between R848 and vehicle treatment for cell line FC1199 with any method of implantation. For cell line KxPxCx, R848 resulted in decreased extra-pancreatic tumor growth, without gross evidence of invasion of lymph nodes, mesentery, liver, or other abdominal structures.
Which is a better agonist for oxaliplatin r848?
It was found that oxaliplatin inhibited the differentiation of MDSCs into M1-like macrophages while TLRs 7/8 agonist, R848 reversed this mis-regulatory effect of oxaliplatin on MDSCs and enhanced the cytotoxic effect of oxaliplatin against cancer cells.
What are the effects of r848 on the immune system?
In vivo, tumors from two of three cell lines were R848-sensitive, resulting in smaller tumor mass, increased immune complexity, increased CD8 + T-cell infiltration and activity, and decreased Treg frequency.
How is r848 used in the treatment of cachexia?
These studies indicate immune-enhancing approaches including R848 may be useful in PDAC and cancer-associated cachexia. With recent advances in the field of cancer immunotherapy, a number of highly effective therapies were developed to enhance anti-tumor immunity.