| RRC ID |
78862
|
| 著者 |
Thierry S, Maadadi S, Berton A, Dimier L, Perret C, Vey N, Ourfali S, Saccas M, Caron S, Boucard-Jourdin M, Colombel M, Werle B, Bonnin M.
|
| タイトル |
TL-532, a novel specific Toll-like receptor 3 agonist rationally designed for targeting cancers: discovery process and biological characterization.
|
| ジャーナル |
Microb Cell
|
| Abstract |
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.
|
| 巻・号 |
10(6)
|
| ページ |
117-132
|
| 公開日 |
2023-6-5
|
| DOI |
10.15698/mic2023.06.797
|
| PII |
MIC0272E140
|
| PMID |
37275475
|
| PMC |
PMC10236204
|
| リソース情報 |
| ヒト・動物細胞 |
TUHR14TKB(RCB138) |
