CD47 related compositions and methods for treating immunological diseases and disorders
Provide herein are fusion polypeptides that comprise a CD47 extracellular domain or a variant thereof that is fused to a Fc polypeptide. The fusion polypeptides are useful for treating an immunological disease or disorder in a subject according to the methods described herein. The fusion polypeptides are capable of suppressing immunoresponsiveness of an immune cell, inhibiting production of proinflammatory cytokines, including inhibiting immune complex-induced production of cytokines.
1. A formulation comprising a fusion polypeptide having the amino acid sequence set forth in SEQ ID NO:39 and a pharmaceutically suitable carrier in which mannitol is present in an amount of at least 1% w/v.
2. The formulation of claim 1 further comprising a buffering agent, wherein the buffering agent is histidine.
3. The formulation of claim 2 wherein mannitol is present in an amount of about 3% w/v.
4. The formulation of claim 1 , wherein the fusion polypeptide forms a dimer of two fusion polypeptide monomers, and wherein the dimer comprises a disulfide bond between each of the extracellular CD47 domain moieties of each of the two fusion polypeptide monomers.
5. The formulation according to claim 4 wherein the disulfide bond between each of the extracellular domain moieties is formed between a cysteine residue of each extracellular CD47 domain moiety, which cysteine residue of each extracellular CD47 domain moiety is most proximal to the amino terminus.
6. The formulation according to claim 5 wherein the fusion polypeptide retains the capability to bind at least one CD47 ligand selected from SIRP-α, SIRPbeta-2, thrombospondin-1, α v β 3 integrin, and α 2 β 1 integrin.