MODULATION OF INNATE IMMUNITY IN THE TREATMENT OF INFLAMMATION-DRIVEN AND INFECTION-DRIVEN DISEASE

Oreola Donini

Research & Development, Soligenix, Inc., New Jersey, USA

Abstract

Innate immunity is a major player in the acute inflammatory response as well as in the immediate defense against infections. Innate Defense Regulators (IDRs) are a novel class of synthetic peptides that enhance the control of microbial infections while attenuating tissue damage and suppressing inflammation. IDRs act downstream of Toll-like receptors by binding to an intracellular adaptor protein, sequestosome-1, that is involved in the transmission of information during intracellular signal transduction, receptor trafficking, protein turnover and bacterial clearance. The lead IDR, dusquetide, has been demonstrated to be safe and efficacious in Phase 1 and 2 clinical studies. Specifically, dusquetide reduced the duration of severe oral mucositis in head and neck cancer patients receiving chemoradiation therapy, while also decreasing the incidence of bacterial infections in this patient population. Oral mucositis is believed to be driven by a dysregulated innate inflammatory response to the damage caused by both radio- and chemotherapy. These results demonstrate the utility of targeting the innate immune system, including: 1) indicating the translatability of innate immune studies in rodents to humans; 2) confirming the role of innate immunity in the pathogenesis of oral mucositis; and 3) illustrating that innate immune modulation can simultaneously increase anti-infective activity, while also modulating inflammation.

Keywords: Innate immunity, oral mucositis, dusquetide, innate defense regulator, anti-infective, anti-inflammatory.