Polynucleotide constructs, pharmaceutical compositions and methods for targeted downregulation of angiogenesis and anticancer therapy
First Claim
1. A method of inducing apoptosis of an endothelial cell in a tumor of a subject in need thereof, the method comprising administering to the subject a nucleic acid construct comprising:
- (a) a first polynucleotide region encoding a chimeric polypeptide including a ligand binding domain of TNF Receptor 1 (TNFR1) fused to an effector domain of Fas; and
(b) a second polynucleotide region comprising a PPE-1-3X promoter, which directs expression of said chimeric polypeptide in the endothelial cell in the tumor;
wherein said chimeric polypeptide, when expressed, induces apoptosis of the endothelial cell in the tumor of said subject and wherein the nucleic acid construct is administered systemically or locally.
1 Assignment
0 Petitions
Accused Products
Abstract
A novel nucleic acid construct for down-regulating angiogenesis in a tissue of a subject is provided. The nucleic acid construct includes: (a) a first polynucleotide region encoding a chimeric polypeptide including a ligand binding domain fused to an effector domain of an apoptosis signaling molecule; and (b) a second polynucleotide region encoding a cis acting regulatory element being for directing expression of the chimeric polypeptide in a specific tissue or cell; wherein the ligand binding domain is selected such that it is capable of binding a ligand present in the specific tissue or cell, whereas binding of the ligand to the ligand binding domain activates the effector domain of the apoptosis signaling molecule. Also provided are methods of utilizing this nucleic acid construct for treating diseases characterized by excessive or aberrant neo-vascularization or cell growth.
-
Citations
26 Claims
-
1. A method of inducing apoptosis of an endothelial cell in a tumor of a subject in need thereof, the method comprising administering to the subject a nucleic acid construct comprising:
-
(a) a first polynucleotide region encoding a chimeric polypeptide including a ligand binding domain of TNF Receptor 1 (TNFR1) fused to an effector domain of Fas; and (b) a second polynucleotide region comprising a PPE-1-3X promoter, which directs expression of said chimeric polypeptide in the endothelial cell in the tumor; wherein said chimeric polypeptide, when expressed, induces apoptosis of the endothelial cell in the tumor of said subject and wherein the nucleic acid construct is administered systemically or locally. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 24, 25, 26)
-
-
18. A method of inducing apoptosis of an endothelial cell in a tumor of a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a nucleic acid construct and a pharmaceutically acceptable carrier
wherein the nucleic acid construct comprises: -
(a) a first polynucleotide region encoding a chimeric polypeptide comprising an extracellular domain of TNFR1 fused to a trans-membrane region and an intracellular region of Fas; and (b) a second polynucleotide region comprising a PPE-1-3X promoter, which directs expression of said chimeric polypeptide in the endothelial cell in the tumor; wherein said pharmaceutical composition induces apoptosis of the endothelial cell in the tumor of the subject and wherein the pharmaceutical composition is administered systemically or locally. - View Dependent Claims (19, 20)
-
-
21. A method of reducing a tumor size in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a nucleic acid construct and a pharmaceutically acceptable carrier,
wherein the nucleic acid construct comprises: -
(a) a first polynucleotide region encoding a chimeric polypeptide comprising an extracellular domain of TNFR1 fused to a trans-membrane region and an intracellular region of Fas; and (b) a second polynucleotide region comprising a PPE-1-3X promoter, which directs expression of said chimeric polypeptide in the tumor; wherein said pharmaceutical composition reduces the tumor size in the subject and wherein the pharmaceutical composition is administered systemically or locally. - View Dependent Claims (22, 23)
-
Specification