Compositions and methods for activating stimulator of interferon gene-dependent signalling
The present invention provides highly active cyclic-di-nucleotide (CDN) immune stimulators that activate DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the CDNs of the present invention are provided in the form of a composition comprising one or more cyclic purine dinucleotides induce STING-dependent type I interferon production, wherein the cyclic purine dinucleotides present in the composition are substantially pure 2′,5′,2′,5′ and 2′,5′,3′,5′ CDNs, and preferably Rp,Rp stereoisomers thereof.
1. A compound of the formula
where R 1 and R 2 are each H,
or a pharmaceutically acceptable salt thereof.
2. A pharmaceutical composition:
a compound according to claim 1 formulated with a pharmaceutically acceptable carrier.
3. The pharmaceutical composition according to claim 2 , wherein the pharmaceutical acceptable carrier comprises one or more agents selected from the group consisting of lipids, interbilayer crosslinked multilamellar vesicles, biodegradeable poly(D,L-lactic-co-glycolic acid) [PLGA]-based or poly anhydride-based nanoparticles or microparticles, and nanoporous particle-supported lipid bilayers.
4. A composition comprising:
a compound according to claim 1 and one or more antigens selected for purposes of inducing an immune response against the antigen(s) when the composition is administered to an individual.
5. A method of inducing stimulator of interferon genes protein (STING)-dependent type I interferon production in an individual in need thereof, comprising:
administering a compound according to claim 1 to the individual in an amount sufficient to induce STING-dependent type I interferon production.
6. The method according to claim 5 , wherein the administration is directly into a tumor mass.