Revisiting Coley's Toxins: Immunogenic Cardiolipins from Streptococcus pyogenes .
Yern-Hyerk ShinSunghee BangSung-Moo ParkXiao MaChelsi CassillyDaniel GrahamRamnik XavierJon ClardyPublished in: Journal of the American Chemical Society (2023)
Coley's toxins, an early and enigmatic form of cancer (immuno)therapy, were based on preparations of Streptococcus pyogenes . As part of a program to explore bacterial metabolites with immunomodulatory potential, S . pyogenes metabolites were assayed in a cell-based immune assay, and a single membrane lipid, 18:1/18:0/18:1/18:0 cardiolipin, was identified. Its activity was profiled in additional cellular assays, which showed it to be an agonist of a TLR2-TLR1 signaling pathway with a 6 μM EC 50 and robust TNF-α induction. A synthetic analog with switched acyl chains had no measurable activity in immune assays. The identification of a single immunogenic cardiolipin with a restricted structure-activity profile has implications for immune regulation, cancer immunotherapy, and poststreptococcal autoimmune diseases.
Keyphrases
- high throughput
- signaling pathway
- toll like receptor
- inflammatory response
- ms ms
- biofilm formation
- immune response
- candida albicans
- rheumatoid arthritis
- papillary thyroid
- single cell
- cell therapy
- nuclear factor
- quality improvement
- squamous cell carcinoma
- pi k akt
- escherichia coli
- pseudomonas aeruginosa
- risk assessment
- mesenchymal stem cells
- cystic fibrosis
- cell proliferation
- lymph node metastasis
- climate change
- childhood cancer