Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: Nov. 7, 2024
Activation of immune receptors, such as Toll-like (TLR), NOD-like (NLR) and Stimulator Interferon Genes (STING) is critical for efficient innate adaptive immunity. Gram-negative bacteria (G-NB) contain multiple TLR, NOD STING agonists. Potential utility G-NB cancer immunotherapy supported by observations tumor regression in the setting infection Coley's Toxins. Coley reported that intravenous (i.v.) administration was likely most effective but produced uncontrollable toxicity. The discovery TLRs their agonists, particularly potent TLR4 agonist lipopolysaccharide (LPS)-endotoxin, comprising ~75% outer membrane G-NB, suggests LPS may be both a active ingredient responsible dose-limiting i.v. toxicity G-NB. This communication reports production killed, stabilized, intact products from non-pathogenic with ~96% reduction LPS-endotoxin activity. One resulting product candidate, Decoy10, resistant to standard methods cell disruption contained TLR2,4,8,9, NOD2 Decoy10 also exhibited reduced mice rabbits, largely uncompromised ability induce cytokine chemokine secretion human cells
Language: Английский