Compositions useful as ligands for the formyl peptide receptor like 1 receptor and methods of use thereof

• US 20060034863A1
• Filed: 07/05/2005
• Published: 02/16/2006
• Est. Priority Date: 10/09/2001
• Status: Active Grant

• Current Assignee: ChemoCentryx, Inc. (Amgen Inc.)
• Original Assignee: ChemoCentryx, Inc. (Amgen Inc.)
• Inventors: Schall, Thomas J., Wei, Zheng, Miao, Zhenhua, Premack, Brett, Howard, Maureen, Berahovich, Robert
• Granted Patent: US 8,637,043 B2
• Time in Patent Office: Days
• US Class Current: 424/190.100
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/523 Beta-chemokines, e.g. RANTES, I-309/TCA-3, MIP-1alpha, MIP-1beta/ACT-2/LD78/SCIF, MCP-1/MCAF, MCP-2, MCP-3, LDCF-1, LDCF-2
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The inventors have discovered that a CKβ8-1 truncation variant, CKβ8-1 (25-116), is a bifunctional ligand for two distinct GPCRs, chemokine receptor CCR1 and formyl peptide receptor like 1 (FPRL1). Hence, the inventors have discovered that, in addition to its functional activity on CCR1, CKβ8-1(25-116) is also a functional ligand for the GPCR receptor FPRL1 that is involved in inflammatory reactions and innate immunity by recruiting monocytes and neutrophils. In addition, the inventors have discovered an alternatively spliced exon of CKβ8-1, named SHAAGtide. SHAAGtide, along with its parent chemokine CKβ8-1 (25-116), is fully functional on both monocytes and neutrophils that are known to express FPRL1. This application relates generally to enhancing immune responses. Such immune responses may be elicited by vaccine administration. Compositions and methods for inducing or enhancing an immune response to an antigen are provided. The compositions and methods are useful for vaccine formulations for therapeutic and prophylactic use (immunization) and for production of antibodies.

Claims

1. A composition for enhancing an immune response to one or more antigens, comprising

at least one polypeptide consisting of from about 10 to about 90 amino acids that includes an amino acid sequence having at least about 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOS:

1, 3, 5, 6, 8, and 11; and

at least one antigen,

wherein the polypeptide enhances the immune response to the antigen and provided that the polypeptide and the antigen are different.

2. The composition of claim 1, comprising at least two different polypeptides.

3. The composition of claim 1, wherein the amino acid sequence is selected from the group consisting of SEQ ID NOS:

1, 3, 5, 6, 8, and 11.

4. The composition of claim 1, wherein the composition is formulated for sustained release.

5. The composition of claim 1, wherein the composition further comprises an adjuvant.

6. The composition of claim 1, wherein the polypeptide consists of from about 10 to about 80 amino acids.

7. The composition of claim 1, wherein the amino acid sequence consists of from about 10 to about 70 amino acids.

8. The composition of claim 1, wherein the amino acid sequence consists of from about 10 to about 60 amino acids.

9. The composition of claim 1, wherein the amino acid sequence consists of from about 10 to about 50 amino acids.

10. The composition of claim 1, wherein the amino acid sequence consists of from about 10 to about 40 amino acids.

11. The composition of claim 1, wherein the amino acid sequence consists of from about 10 to about 30 amino acids.

12. A composition for enhancing an immune response to one or more antigens, comprising

at least one isolated polypeptide consisting of from about 10 to about 90 amino acids that includes an amino acid sequence having at least about 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOS:

1, 5, 6, 8, and 11; and

at least one antigen,

wherein the polypeptide enhances the immune response to the antigen.

13. The composition of claim 12, wherein the polypeptide consists of from about 10 to about 80 amino acids.

14. The composition of claim 12, wherein the amino acid sequence consists of from about 10 to about 60 amino acids.

15. The composition of claim 12, wherein the amino acid sequence consists of from about 10 to about 50 amino acids.

16. The composition of claim 12, wherein the amino acid sequence consists of from about 10 to about 40 amino acids.

17. The composition of claim 12, wherein the amino acid sequence consists of from about 10 to about 30 amino acids.

18. A method for enhancing an immune response to an antigen in a subject comprising:

administering

at least one polypeptide consisting of from about 10 to about 90 amino acids that includes an amino acid sequence having at least about 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOS;

1, 3, 5, 6, 8, and 11; and

at least one antigen;

wherein the polypeptide enhances the immune response to the antigen.

19. A method for enhancing an immune response to an antigen in a subject comprising:

administering

an immune response enhancing fragment of a polypeptide set forth in SEQ ID NO;

16 consisting of from about 10 to about 90 amino acids, wherein said fragment comprises an amino acid sequence at least about 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOS;

1, 3, 5, 6, 8, and 11; and

an antigen.

20. A composition comprising a cell exogenously expressing at least one sequence having at least 90% sequence identity to a nucleic acid sequence selected from the group consisting of SEQ ID NOS:

20, 22, 24, 25, 27, and 30, or fragment thereof.

21. A composition, comprising:

at least one tumor cell; and

at least one cell exogenously expressing at least one sequence having at least 80% sequence identity to a nucleic acid sequence selected from the group consisting of SEQ ID NOS;

20, 22, 24, 25, 27, and 30, or fragment thereof.

22. A kit comprising:

a pharmaceutical composition comprising at lease one polypeptide having at least 80% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOS;

1, 3, 5, 6, 8, and 11, or a fragment thereof, and a pharmaceutically acceptable carrier; and

a syringe.