Revisiting Coley’s Toxins: Immunogenic Cardiolipins from <i>Streptococcus pyogenes</i>
Yern‐Hyerk Shin, Sunghee Bang, Sung‐Moo Park, Xiao Ma, Chelsi D. Cassilly, Daniel B. Graham, Ramnik J. Xavier, Jon Clardy
Abstract
High Resolution Image Download MS PowerPoint Slide 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.