Tweak-pseudomonas exotoxin a fusion protein for cancer therapy
OwnerJeffrey A. Winkles, Sharron Browninventors
Life of this patent
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Abstract
Soluble TNF superfamily ligand monomers, including TWEAK, spontaneously associate into a homotrimeric structure that binds with high affinity to a cell surface receptor(s). A TWEAK is fused with a modified (mutant) Pseudomonas exotoxin (PE38). This fusion protein's TWEAK domain binds with high affinity to a fibroblast growth factor-inducible 14 (Fn14) cell surface receptor. These fusion proteins act as cytotoxins targeting various cells, diseased cells, such as cancer cells, and cells undergoing cellular insult response.
Claims30
A cytotoxin, comprising:
- a tumor necrosis factor like weak inducer of apoptosis (TWEAK) receptor-binding domain fused with a Pseudomonas exotoxin (PE38),
- wherein the TWEAK receptor-binding domain binds with a cell.
A cytotoxin, comprising:
- an amino terminus, the amino terminus including a tumor necrosis factor like weak inducer of apoptosis (TWEAK) receptor-binding domain, fused with a Pseudomonas exotoxin (PE38),
- wherein the TWEAK receptor-binding domain binds with a cell.
A method of inducing death of a cell, comprising:
- contacting the cell with a cytotoxin, the cytotoxin including a tumor necrosis factor like weak inducer of apoptosis (TWEAK) receptor binding domain fused with a mutant Pseudomonas exotoxin (PE38), that binds the TWEAK receptor-binding domain with a cell, inducing cell death.
A method of treating a subject in need thereof, comprising:
- administering a cytotoxin, the cytotoxin including a tumor necrosis factor like weak inducer of apoptosis (TWEAK) receptor-binding domain fused with a Pseudomonas exotoxin (PE38), that binds the TWEAK receptor-binding domain with a cell.
A cytotoxin, comprising:
- an anti-Fn14 antibody associated with a Pseudomonas exotoxin (PE38),
- wherein the anti-Fn14 antibody binds with a cell.
Dependencies are inferred from the claim text.