Peptide tumor cell growth inhibitors

• US 6,110,889 A
• Filed: 05/29/1997
• Issued: 08/29/2000
• Est. Priority Date: 06/14/1996
• Status: Expired due to Term

• 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: Hayashi, Shinichiro, Miller, Edmund J.
• Primary Examiner(s): DAVENPORT, AVIS MICHELLE
• Application Number:
  US08/865,472
• Time in Patent Office: 1,188 Days
• Field of Search: 514/2, 514/17, 530/300, 530/329, 530/351, 424/85.1, 424/85.2, 424/184.1, 424/185.1, 424/277.1
• US Class Current: 514/19.4
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/54 Interleukins [IL]
• CPC Class Codes: C07K 14/5421 IL-8
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids

Abstract

Disclosed are peptide-based compositions and methods for inhibiting and modulating the actions of CXC intercrine molecules. The antileukinate peptides described inhibit IL-8, GRO and MIP2β binding to neutrophils and neutrophil activation. The peptides are particularly advantageous as they inhibit IL-8-induced enzyme release at a 25 fold lower concentration than is required to inhibit chemotaxis, which makes them ideal for treating various inflammatory diseases and disorders including, amongst others, Adult Respiratory Distress Syndrome (ARDS), cystic fibrosis and chronic bronchitis. The invention further includes methods for inhibiting tumor cell growth by employing selected members of the disclosed group of peptides to inhibit α-chemokine binding to the tumor cell.

Claims

1. A method of inhibiting binding of an α

-chemokine to a tumor cell, comprising administering to said cell an amount of a peptide comprising the sequence of SEQ ID NO;

1 effective to inhibit binding of said α

-chemokine.

2. The method of claim 1 wherein the tumor cell is identified as a melanoma cell line.

3. The method of claim 2 wherein the melanoma cell line is further identified as Hs 294T, RPMI-7951, A375P, A375SM, C8161 or WM115.

4. The method of claim 1 wherein the tumor cell is identified as an adenocarcinoma cell.

5. The method of claim 4 wherein the adenocarcinoma cell is further identified as lung adenocarcinoma cell A549, NCI-H441 or SK-LU-1.

6. The method of claim 1 wherein the tumor cell is a squamous lung cancer cell.

7. The method of claim 6 wherein the squamous cell lung cancer cell is further identified as NCI-H292.

8. The method of claim 4 wherein the adenocarcinoma cell is selected from the group consisting of stomach AGS, stomach Hs746T, breast cell MCG-7, prostate DU145 and colon Caco-2.

13. The method of claim 1 wherein the tumor cell is identified as an endothelial cell.

14. The method of claim 13 wherein the endothelial cell is identified as a human umbilical vein endothelial cell.

9. A method of inhibiting growth of a melanoma cell, comprising inhibiting binding of MGSA/Groα

to said cell with an effective amount of a peptide having the amino acid sequence of Arg Arg Trp Trp Cys Arg (SEQ ID NO;

1).

10. The method of claim 9 wherein the growth inhibiting is in vitro.

11. The method of claim 10 wherein the in vitro growth inhibiting effective amount is defined as between about 40 to about 125 μ

M the peptide having the amino acid sequence of SEQ ID NO;

1.

12. The method of claim 11 wherein the effective amount is further defined as between about 50 μ

M and about 100 μ

M of the peptide having the amino acid sequence of SEQ ID NO;

1.