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US 2026/0021177 A1Published application
Immunomodulatory fusion protein-metal hydroxide complexes and methods thereof
AssigneeMassachusetts Institute of Technology
InventorsDarrell J. IRVINE, Karl Dane WITTRUP, Tyson MOYER, Yash AGARWAL
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Abstract
The present disclosure provides immunomodulatory fusion proteins-metal hydroxide complexes comprising an immunomodulatory domain adsorbed to a metal hydroxide via ligand exchange. The disclosure also features compositions and methods of using the same, for example, to treat cancer.
Claims142
An immunomodulatory fusion protein-metal hydroxide complex comprising:
- (a) an immunomodulatory fusion protein comprising
- (i) an immunomodulatory domain,
- (ii) a metal hydroxide-binding peptide comprising at least one kinase target motif of a secretory pathway kinase that comprises at least one phosphorylated amino acid, and
- (iii) optionally, a stabilizing domain;
- and
- (b) a metal hydroxide
- wherein the immunomodulatory fusion protein is adsorbed via ligand exchange to the metal hydroxide via the at least one phosphorylated amino acid of the metal hydroxide-binding peptide, thereby forming an immunomodulatory fusion protein-metal hydroxide complex.
4 more elements
An immunomodulatory fusion protein-metal hydroxide complex comprising:
- (a) an immunomodulatory fusion protein comprising
- (i) an immunomodulatory domain,
- (ii) a metal hydroxide-binding peptide comprising at least one kinase target motif of the secretory pathway kinase Fam20C that comprises the amino acid sequence S-X-E, and
- (iii) optionally, a stabilizing domain;
- and
- (b) a metal hydroxide,
- wherein the at least one kinase target motif of the metal hydroxide-binding peptide comprises a phosphoserine, and wherein the immunomodulatory fusion protein is adsorbed via ligand exchange to the metal hydroxide via the at least one phosphoserine of the metal hydroxide-binding peptide, thereby forming an immunomodulatory fusion protein-metal hydroxide complex.
4 more elements
An immunomodulatory fusion protein-metal hydroxide complex comprising:
- (a) an immunomodulatory fusion protein comprising
- (i) an immunomodulatory domain, optionally linked to a stabilizing domain;
- (ii) a terminal metal hydroxide-binding peptide comprising one or more hydroxyl replacement groups that is coupled, optionally via a linker, by a protein-reactive moiety;
- and
- (b) a metal hydroxide,
- wherein the immunomodulatory fusion protein is adsorbed via ligand exchange to the metal hydroxide via the at least one hydroxyl replacement groups of the metal hydroxide-binding peptide, thereby forming an immunomodulatory fusion protein-metal hydroxide complex.
3 more elements
An immunomodulatory fusion protein comprising:
- (a) an immunomodulatory domain,
- (b) a metal hydroxide-binding peptide comprising at least one kinase target motif of the secretory pathway kinase Fam20C that comprises the amino acid sequence S-X-E, wherein X is any amino acid, optionally wherein X is E, S, V, H, Q, or G;
- (c) optionally, a stabilizing domain;
- and
- wherein the at least one kinase target motif of the metal hydroxide-binding peptide comprise a serine that is modified with a phosphate group, and wherein the immunomodulatory fusion protein undergoes ligand exchange with alum via the at least one phosphoserine of the metal hydroxide-binding peptide, thereby coupling the immunomodulatory fusion protein to alum to form an immunomodulatory fusion protein-metal hydroxide complex.
2 more elements
An immunomodulatory fusion protein comprising:
- (a) an immunomodulatory domain, optionally linked to a stabilizing domain;
- and
- (b) a metal hydroxide-binding peptide comprising one or more phosphorylated amino acids that is coupled, optionally via a linker, by a protein-reactive moiety,
- wherein the immunomodulatory fusion protein undergoes ligand exchange with alum via the at least one hydroxyl replacement groups of the metal hydroxide-binding peptide, thereby coupling the immunomodulatory fusion protein to alum to form an immunomodulatory fusion protein-metal hydroxide complex.
1 more element
A method for increasing phosphorylation of an immunomodulatory fusion protein, the method comprising contacting a cell with:
- (a) a nucleotide sequence encoding an immunomodulatory fusion protein comprising:
- an immunomodulatory domain,
- a metal hydroxide-binding peptide comprising one or more kinase target motif,
- optionally, a stabilizing domain;
- and
- (b) a nucleotide sequence encoding a kinase comprising:
- an ER targeting leader sequence operably linked to
- a kinase domain operably linked to
- an anchor peptide
- wherein the kinase is localized to the secretory pathway and wherein the one or more kinase target motifs of the metal hydroxide-binding peptide are phosphorylated by the kinase in the secretory pathway, thereby increasing phosphorylation of the immunomodulatory fusion protein.
7 more elements
A method for increasing phosphorylation of an immunomodulatory fusion protein comprising
- (i) an immunomodulatory domain,
- (ii) a metal hydroxide-binding peptide comprising one or more kinase target motifs of the secretory pathway kinase Fam20C, and
- (iii) optionally a stabilizing domain,
- the method comprising contacting a cell with an expression vector comprising a nucleic acid encoding the immunomodulatory fusion protein and an expression vector comprising a nucleic acid encoding the secretory pathway kinase Fam20C operably linked to an anchor peptide, wherein the secretory pathway kinase Fam20C is localized to the secretory pathway by the anchor peptide, and wherein the one or more kinase target motifs are phosphorylated by Fam20C in the secretory pathway, thereby increasing phosphorylation of the immunomodulatory fusion protein.
1 more element
Dependencies are inferred from the claim text.