| Autor: |
Sylvain Thierry, Sarah Maadadi, Aurore Berton, Laura Dimier, Clémence Perret, Nelly Vey, Saïd Ourfali, Mathilde Saccas, Solène Caron, Mathilde Boucard-Jourdin, Marc Colombel, Bettina Werle, Marc Bonnin |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Microbial Cell, Vol 10, Iss 06, Pp 117-132 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2311-2638 |
| DOI: |
10.15698/mic2023.06.797 |
| Popis: |
Toll-like receptor 3 (TLR3) is an innate immune receptor that recognizes double-stranded RNA (dsRNA) and induces inflammation in immune and normal cells to initiate anti-microbial responses. TLR3 acts also as a death receptor only in cancer cells but not in their normal counterparts, making it an attractive target for cancer therapies. To date, all of the TLR3-activating dsRNAs used at preclinical or clinical stages have major drawbacks such as structural heterogeneity, toxicity, and lack of specificity and/or efficacy. We conducted the discovery process of a new family of TLR3 agonists that are chemically manufactured on solid-phase support and perfectly defined in terms of sequence and size. A stepwise discovery process was performed leading to the identification of TL-532, a 70 base pair dsRNA that is potent without transfection reagent and is highly specific for TLR3 without activating other innate nucleic sensors such as RIG-I/MDA5, TLR7, TLR8, and TLR9. TL-532 induces inflammation in murine RAW264.7 myeloid macrophages, in human NCI-H292 lung cancer cells, and it promotes immunogenic apoptosis in tumor cells in vitro and ex vivo without toxicity towards normal primary cells. In conclusion, we identified a novel TLR3 agonist called TL-532 that has promising anticancer properties. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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