Stimuler la réponse interféron de type I avec des petites molécules : le renouveau d’une vieille idée

Abstract

Type I interferons play a central role in the establishment of an innate immune response against viral infections and tumor cells. Shortly after their discovery in 1957, several groups have looked for small molecules capable of inducing the expression of these cytokines with therapeutic applications in mind. A set of active compounds in mice were identified, but because of their relative inefficiency in humans for reasons not understood at the time, these studies fell into oblivion. In recent years, the characterization of pathogen recognition receptors and the signaling pathways they activate, together with the discovery of plasmacytoid dendritic cells, have revolutionized our understanding of innate immunity. These discoveries and the popularization of high-throughput screening technologies have renewed the interest for small molecules that can induce type I interferons. Proofs about their therapeutic potency in humans are expected very soon.

Identification of a small molecule that primes the type I interferon response to cytosolic DNA

“…The quest for small compounds activating the type I interferon response is a field of intense researches in academic laboratories and pharmaceutical companies 9–18 , and some molecules are already marketed or in advanced clinical trials 19, 20 . Compounds from imidazoquinoline family, such as resiquimod (R848) and imiquimod (R837), are well-known inducers of the IFN response that bind TLR7, TLR8 or both 21 .…”