Methods of treating cytokine release syndrome by administering a molecule comprising a soluble tandem selectin glycoprotein ligand
View Patent ↗Methods of using soluble tandem selectin glycoprotein ligand (TSGL) and TSGL fusion proteins, such as TSGL-Ig, for therapeutic treatment of cancers, including in combination with T cell activation therapies or an adoptive cell transfer (ACT) therapy.
1 . A method of treating cytokine release syndrome (CRS), comprising administering an effective amount of a molecule to a subject in need thereof, wherein the molecule comprises a soluble tandem selectin glycoprotein ligand (TSGL) peptide comprising two or more PSGL-1 domains, and wherein each of the two or more PSGL-1 domains comprises amino acids 5 to 16 of SEQ ID NO: 2, wherein the molecule is administered in an amount effective to reduce the elevation of von Willebrand Factor or Angiopoietin-2 serum concentration.
2 . The method of claim 1 , wherein the molecule contains at least one sialyl Lewis X (sLe x ) tetrasaccharide.
3 . The method of claim 2 , wherein the molecule is administered prior to use of an adoptive cellular therapy.
4 . The method of claim 2 , wherein the molecule is administered simultaneously with use of an adoptive cellular therapy.
5 . The method of claim 3 , wherein the adoptive cellular therapy comprises the administration of an immune cell population that has been genetically transformed with a chimeric antigen receptor.
6 . The method of claim 4 , wherein the adoptive cellular therapy comprises the administration of an immune cell population that has been genetically transformed with a chimeric antigen receptor.
7 . The method of claim 1 , wherein the TSGL peptide is fused to a non-TSGL polypeptide to form a fusion peptide molecule, wherein the non-TSGL polypeptide is an immunoglobulin Fc.
8 . The method of claim 7 , wherein the fusion peptide molecule contains at least one sialyl Lewis X (sLe x ) tetrasaccharide.
9 . A method of treating cytokine release syndrome (CRS), comprising administering an amount of a molecule to a subject in need thereof, wherein the molecule comprises a soluble tandem selectin glycoprotein ligand (TSGL) peptide comprising two or more PSGL-1 domains, and wherein each of the two or more PSGL-1 domains comprises amino acids 10 to 16 of SEQ ID NO: 2, wherein the molecule is administered in an amount effective to reduce the elevation of von Willebrand Factor or Angiopoietin-2 serum concentration.
10 . The method of claim 9 , wherein the molecule contains at least one sialyl Lewis X (sLe x ) tetrasaccharide.
11 . The method of claim 10 , wherein the molecule is administered prior to use of an adoptive cellular therapy.
12 . The method of claim 10 , wherein the molecule is administered simultaneously with use of an adoptive cellular therapy.
13 . The method of claim 11 , wherein the adoptive cellular therapy comprises the administration of an immune cell population that has been genetically transformed with a chimeric antigen receptor.
14 . The method of claim 12 , wherein the adoptive cellular therapy comprises the administration of an immune cell population that has been genetically transformed with a chimeric antigen receptor.
15 . The method of claim 9 , wherein the TSGL peptide is fused to a non-TSGL polypeptide to form a fusion peptide molecule, wherein the non-TSGL polypeptide is an immunoglobulin Fc.
16 . The method of claim 15 , wherein the fusion peptide molecule contains at least one sialyl Lewis X (sLe x ) tetrasaccharide.