Trail compositions with reduced immunogenicity
AssigneeTheraly Fibrosis, Inc.
InventorsAlex Sokoloff, Viktor Roschke, Kang Choon Lee, Seulki Lee, Yumin Oh
Life of this patent
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Abstract
Fusion polypeptides with modified multimerization domains that provide high expression, solubility, stability, and low immunogenicity to the fusion polypeptides have been developed. TRAIL compositions with the modified multimerization domains show improved physico-chemical and biological properties relative to TRAIL compositions with unmodified multimerization domains. The TRAIL compositions also have lower immunogenicity in the mammalian host when compared to that of TRAIL compositions with unmodified multimerization domains. The TRAIL compositions induce apoptosis of cancer cells and cancer-associated fibroblasts in vivo, reducing tumor size.
Claims35
A recombinant fusion polypeptide comprising a first amino acid sequence comprising an amino acid sequence having at least 90% identity to any one of SEQ ID NOs:
- 4-8,
- wherein at least one of the amino acids at positions 14, 17, and 26 of SEQ ID NOs:
- 4-8 is selected from the group consisting of Valine (V), Glutamic acid (E), and/or Glutamine (Q), and wherein immunogenic epitopes of Isoleucine at position 17 and Lysine at position 26 are not present together in the first amino acid sequence, and
- a second amino acid sequence comprising a tumor necrosis factor-related apoptosis ligand (TRAIL) domain.
A recombinant fusion polypeptide comprising a first amino acid sequence selected from SEQ ID NOs:
- 4-8 and a second amino acid sequence comprising a TRAIL domain.
Dependencies are inferred from the claim text.