EGF receptor epitope peptides and uses thereof

• US 20050255555A1
• Filed: 02/17/2005
• Published: 11/17/2005
• Est. Priority Date: 02/20/2004
• Status: Active Grant

• Current Assignee: Commonwealth Scientific & Industrial Research Organisation (Commonwealth Of Australia As Represented By Department Of Industry, Innovation, Climate Change, Science, Research And Tertiary Education), Ludwig Institute for Cancer Research, Ltd.
• Original Assignee: Commonwealth Scientific & Industrial Research Organisation (Commonwealth Of Australia As Represented By Department Of Industry, Innovation, Climate Change, Science, Research And Tertiary Education)
• Inventors: Scott, Andrew Mark, Old, Lloyd J., Johns, Terrance Grant, Burgess, Antony Wilks, Wittrup, K. Dane, Adams, Timothy E., Chao, Ginger
• Granted Patent: US 7,767,792 B2
• Time in Patent Office: Days
• US Class Current: 435/69.100
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators

Abstract

The present invention relates generally to growth factor receptor epitope peptides, particularly EGF family receptor epitope peptides. The invention also relates to the use of the receptor peptides in generating antibodies which have anti-tumor or anti-cancer activity or in stimulating an immunological response. The invention further relates to antibodies specifically directed against the receptor peptides. Methods for generating an immune response and for treatment of tumors and cancer are also provided.

Claims

1. An isolated receptor polypeptide which comprises the amino acid sequence set out in any of SEQ ID NOS:

1-14 and immunogenic fragments thereof.

2. An isolated peptide having the amino acid sequence CGADSYEMEEDGVRKC (SEQ ID NO:

1).

3. An isolated peptide having the amino acid sequence CGADSYEMEEDGVRK (SEQ ID NO:

2).

4. An isolated peptide having the amino acid sequence CGPDYYEVEEDGIRKC (SEQ ID NO:

3).

5. An isolated peptide having the amino acid sequence CNTDTYEVEENGVRKC (SEQ ID NO:

4).

6. An isolated peptide having the amino acid sequence CGPDSYEVEEDGVRKC (SEQ ID NO:

5).

7. An isolated peptide having the amino acid sequence CSSDSYEVEEDGVRKC (SEQ ID NO:

6).

8. An isolated peptide having the amino acid sequence CGADSYEMEEDAVRKC (SEQ ID NO:

7).

9. An isolated peptide having the amino acid sequence CPLHNQEVTAEDGTQRC (SEQ ID NO:

8).

10. An isolated peptide having the amino acid sequence CPPDKMEVDKNGLKMC (SEQ ID NO:

9).

11. An isolated peptide having the amino acid sequence CPSSKMEVEENGIKMC (SEQ ID NO:

10).

12. An isolated peptide having an amino acid sequence:

13. An isolated peptide having an amino acid sequence:

14. An isolated peptide having an amino acid sequence:

15. An isolated peptide having an amino acid sequence:

16. An isolated nucleic acid which encodes the peptide set out in any of SEQ ID NOS:

1-14.

17. An immunogenic receptor peptide, wherein said peptide is selected from one or more of any of SEQ ID NOS:

1-14, or an immunogenic fragment thereof.

18. A method for immunizing a mammal comprising administering an growth factor receptor epitope peptide or an immunogenic fragment thereof, whereby antibodies which are immunoreactive with the epitope peptide exposed on cells expressing abnormal or overexpressed growth factor receptor, but not exposed on wild type cells, are produced.

19. A method for immunizing a mammal comprising administering an-EGF receptor peptide selected from any of SEQ ID NOS:

1-14 or an immunogenic fragment thereof, whereby antibodies which are immunoreactive with the epitope peptide exposed on cells expressing abnormal or overexpressed EGFR, but not exposed on wild type cells, are produced.

20. A vaccine comprising one or more EGFR peptide selected from any of SEQ ID NOS:

1-14, and a pharmaceutically acceptable adjuvant.

21. An immogenic composition comprising one or more EGFR peptide selected from any of SEQ ID NOS:

1-14, and a pharmaceutically acceptable adjuvant.

22. A tumor or anti-cancer vaccine comprising one or more EGF family receptor peptides selected from the group of any of SEQ ID NOS:

1-14 and a pharmaceutically acceptable adjuvant, further comprising one or more additional tumor antigens.

23. The vaccine of claim 22, wherein said tumor antigen is an EGF or EGFR antigens.

24. A vaccine for treatment of a mammal, subject suffering from head and neck cancer, breast cancer, or prostate tumors and glioma comprising an immunogenic amount of one or more EGF family receptor peptides selected from the group of any of SEQ ID NOS:

1-14 or immunogenic fragment thereof, and a pharmaceutically acceptable adjuvant.

25. The vaccine of claim 24, wherein said peptide is conjugated to a carrier.

26. A pharmaceutical composition comprising an EGF family receptor peptide selected from one or more of peptides selected from any of SEQ ID NOS:

1-14, and a pharmaceutically acceptable carrier

27. A pharmaceutical composition comprising an EGF family receptor peptide antibody immunoreactive with one or more of peptides selected from any of SEQ ID NOS:

1-14, and a pharmaceutically acceptable carrier.

28. A purified antibody to an EGF family receptor peptide selected from any of SEQ ID NOS:

1-14.

29. The antibody of claim 28, wherein said antibody is a monoclonal antibody.

30. The antibody of claim 28, wherein said antibody is labeled with a detectable label.

31. The antibody of claim 28, wherein said antibody is covalently attached to or otherwise associated with one or more other molecule or agent having a therapeutic or diagnostic purpose.

31-1. A method for generating antibodies immunoreactive with an epitope exposed on cells expressing abnormal or overexpressed EGFR, but not exposed on wild type cells, comprising immunizing an animal with an EGF receptor peptide selected from any of SEQ ID NOS:

1-14 or a fragment thereof and isolating peptide binding antibodies.

32. The antibody of claim 31 wherein the other molecules or agents are selected from other antibodies or antibody fragments with distinct characteristics, toxins, ligands, radioactive isotopes and chemotherapeutic agents.

32-2. A method for selecting antibodies immunoreactive with an epitope exposed on cells expressing abnormal or overexpressed EGFR, but not exposed on wild type cells, comprising screening candidate antibodies or cells expressing antibodies or active antibody fragments with an EGF receptor peptide selected from any of SEQ ID NOS:

1-14 or a fragment thereof.

33. A nucleic acid vaccine or DNA vaccine comprising nucleic acids encoding immunogenic EGF family receptor peptides, particularly selected from any of SEQ ID NOS:

1-14.

34. The vaccine of claim 33, further comprising a nucleic acid encoding a tumor antigen or immunomodulatory molecule peptide.

35. A method for determining and monitoring tumors and cancer including head and neck cancer, breast cancer, or prostate tumors and glioma by detecting the presence or exposure of an EGF receptor epitope peptide selected from the group of any of SEQ ID NOS:

1-14.

36. The method of claim 35, wherein the EGF receptor epitope peptide is measured by:

b. contacting a sample in which the presence or exposure of an EGF receptor epitope peptide selected from the group of any of SEQ ID NOS;

1-14 is suspected with an antibody to the said EGF receptor peptide under conditions that allow binding of the peptide to the antibody to occur; and

b. detecting whether binding has occurred between the EGF receptor epitope peptide from the sample and the antibody;

wherein the detection of binding indicates the presence or exposure of the EGF receptor epitope peptide in the sample.

37. A method of inducing an immune response in a subject which has tumors or cancer including head and neck cancer, breast cancer, lung cancer, ovarian cancer, bladder cancer, laryngeal cancer, squamous cell carcinoma, or prostate tumors and glioma comprising administering to the subject an amount of the pharmaceutical composition comprising an EGF receptor epitope peptide selected from the group of any of SEQ ID NOS:

1-14, and a pharmaceutically acceptable carrier, thereby inducing an immune response.