Drug intelligence / Profile preview

dmLT

Development stage
Phase 2
Lead developer
PATH
Modality
Recombinant Proteins and Enzymes, Liposomes → Lipid-based Nanoparticles → Nanoparticles → Drug Delivery Systems
Administration
Mucosal, Parenteral
01

Overview

dmLT (double mutant heat-labile enterotoxin, also known as LT(R192G/L211A)) is a genetically detoxified derivative of the *Escherichia coli* heat-labile enterotoxin (LT) developed for use as a vaccine adjuvant. It is an 84-kDa polymeric protein with an AB5 structure composed of an enzymatically active A subunit and a pentameric B subunit. The two mutations in the A subunit (R192G and L211A) reduce toxicity while preserving immunostimulatory properties. dmLT enhances both systemic and mucosal immune responses to co-administered antigens when delivered via mucosal or parenteral routes. Its mechanism involves receptor binding by the B subunit to facilitate cellular entry and antigen transport across mucosal surfaces, while the A subunit ADP-ribosylates Gsα proteins leading to cAMP accumulation that promotes dendritic cell activation, cytokine secretion, and induction of Th17 cells[6][8]. Unlike its parent molecule LT, dmLT does not cause significant epithelial cAMP intoxication or intestinal fluid secretion[6].

Other names
double mutant heat-labile enterotoxindouble mutant LT
02

Targets

GNASGM1 (GM1 ganglioside)

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