Methods for treating cancer targeting transglutaminase

• US 8,299,040 B2
• Filed: 10/05/2007
• Issued: 10/30/2012
• Est. Priority Date: 10/18/2006
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Mehta, Kapil, Lopez-Berestein, Gabriel, Sood, Anil, Verma, Amit, Guha, Sushovan, Fok, Jansina
• Primary Examiner(s): McGarry, Sean
• Application Number:
  US11/867,717
• Publication Number:
  US 20080279844A1
• Time in Patent Office: 1,852 Days
• Field of Search: None
• US Class Current: 514/44.A
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 9/1044 Protein-glutamine gamma-glutamyltransferase (2.3.2.13), i.e. transglutaminase or factor XIII
• CPC Class Codes: C12Y 203/02013 Protein-glutamine gamma-glutamyltransferase (2.3.2.13), i.e. transglutaminase or factor XIII
• CPC Class Codes: C12Y 207/11013 Protein kinase C (2.7.11.13)

Abstract

A method for treating cancer comprising inhibiting transglutaminase activity is provided. Suitable cancer types for which the methods of the present disclosure can be used to treat include, but are not limited to, pancreatic, breast, and ovarian cancers and melanoma. The inhibition of transglutaminase activity may be performed by one or more techniques, including, but not limited to, downregulating transglutaminase expression, inhibiting TG2 translation, or blocking TG2 enzymatic activity, such as with a small molecule inhibitor or intracellular antibody (intrabody).

Claims

1. An isolated siRNA that inhibits the expression of TG2 wherein the siRNA is targeted to at least one of the sequences defined by SEQ ID NO:

19 one having 90 percent homology thereto.

2. An expression vector useful in inhibiting TG2 expression and constitutive activation of NF-κ

B comprising isolate siRNA targeted to at least one of the sequences defined by SEQ ID NO;

19 or one having 90 percent homology thereto.

3. A method of modulating drug resistance in a cancer patient in need thereof comprising the step of administering to the patient a therapeutically effective amount of TG2-specific siRNA, wherein the expression of TG2 and the constitutive activation of NF-κ

B are inhibited by isolated siRNA targeted to at least one of the sequences defined by SEQ ID NO;

19 or SEQ ID NO;

20, or one having 90 percent homology thereto.

4. A method of treating metastasis in a cancer patient in need thereof comprising the step of administering to the patient a therapeutically effective amount of TG2-specific siRNA, wherein the expression of TG2 and the constitutive activation of NF-κ

B are inhibited by isolated siRNA targeted to at least one of the sequences defined by SEQ ID NO;

19 or SEQ ID NO;

20, or one having 90 percent homology thereto.

5. A method of treating cancer in a patient in need thereof comprising the step of administering to the patient a therapeutically effective amount of TG2-specific siRNA, wherein the expression of TG2 and the constitutive activation of NF-κ

B are inhibited by isolated siRNA targeted to at least one of the sequences defined by SEQ ID NO;

19 or SEQ ID NO;

20, or one having 90 percent homology thereto.

6. The method of claim 5 wherein the cancer is breast cancer, melanoma, pancreatic cancer or ovarian cancer.