Genes differentially expressed in cancer cells to design cancer vaccines

• US 20020018766A1
• Filed: 04/05/2001
• Published: 02/14/2002
• Est. Priority Date: 10/05/1998
• Status: Abandoned Application

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Nicolette, Charles A., Shankara, Srinivas, Roberts, Bruce L.
• Application Number:
  US09/826,609
• Publication Number:
  US 20020018766A1
• Time in Patent Office: Days
• US Class Current: 424/93.21
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity

Abstract

The present invention calls utilized genes differentially expressed in target cells to design vaccines to generate an immune response. Unlike prior art methods that seek to identify antigenic proteins from phenotypic analysis, the subject method applies functional genomics for antigen identification. The method is exemplified herein and therefore provides compositions and methods for inducing an immune response against gp 100 melanoma cells and for inducing an immune response against HER-2⁺cells. Cancer vaccines and adoptive immunotherapeutic methods to treat and prevent conditions associated with the presence of these cells in a subject also are provided. The methods can be practiced by administering the appropriate gene or cancer vaccine, antibody, protein, polypeptide, antigen-presenting cell or immune effector cell.

Claims

1. A method to identify a putative cancer therapeutic comprising the steps of:

(a) identifying a polynucleotide which is uniquely expressed or overexpressed in a target cancer cell as compared with a control non-cancer cell;

(b) determining the protein corresponding to said identified polynucleotide;

(c) determining if said protein, or fragment thereof, is immunogenic,

wherein the ability of said protein to elicit an immune response against said target cancer cell is indicative of a putative cancer therapeutic.

2. The method of claim 1, wherein said immunogenic protein, or fragement thereof, is administered to a subject in a gene delivery vehicle.

3. The method of claim 1, wherein said immunogenic protein, or fragment thereof, is administered to a subject in an antigen presenting cell.

4. The method of claim 1, further comprising the steps of

(a) generating immune effector cells reactive with an immunogenic protein, and

(b) determining if said immune effector cells are immunogenic,

wherein the ability of said immune effector cells to elicit an immune response against said target cancer cell is indicative of a putative cancer therapeutic.

5. The method of claim 1, further comprising the steps of

(a) generating antibodies reactive with an immunogenic protein and,

(b) determining if said antibodies are immunogenic,

wherein the ability of said antibodies to elicit an immune response against said target cancer cell is indicative of a putative cancer therapeutic.

6. The method of claim 5, wherein said antibodies are monoclonal antibodies.

7. A method to design a cancer vaccine from a sample obtained from a subject suffering from cancer, the improvement comprising:

identifying an amino acid sequence which is not previously known to be antigenic, but which is (i) uniquely expressed or overexpressed in a target cancer cell from said subject, as compared with a control non-cancer cell, and

(ii) capable of eliciting an immune response against said target cancer cell.

8. A method for inducing an immune response against a target cell in a subject, comprising delivering to the subject an effective amount of an antigenic peptide that is uniquely expressed or overexpressed in the target cell and has not been previously identified as having the ability to induce an immune response in the subject, whereby an immune response is mounted against the target cell.

9. The method of claim 8, wherein the peptide is delivered as a sequence of amino acids.

10. The method of claim 8, wherein the peptide is delivered as a polynucleotide that encodes the antigenic peptide.

11. The method of claim 8, wherein the uniquely or overexpressed polynucleotide is identified by the method comprising:

(a) obtaining a set of polynucleotides representing gene expression in a target cell;

(b) obtaining a set of polynucleotides representing gene expression in a control cell;

(c) identifying a unique or overexpressed polynucleotide in the target cell as compared to the control cell; and

(d) identifying a unique or overexpressed polynucleotide which is capable of eliciting an immune response in the subject.

12. The method of claim 8, further comprising administering an effective amount of a cytokine and/or co-stimulatory molecule to the subject.

13. The method of claim 10, wherein the polynucleotide is administered to the subject in a gene delivery vehicle.

14. The method of claim 10, wherein the polynucleotide is administered to the subject in a host cell.

15. The method of claim 14, wherein the host cell is a antigen presenting cell.

16. The method of claim 14 or 15, further comprising administering an effective amount of a cytokine and/or co-stimulatory molecule to the subject.

18. The method of claim 17, wherein the uniquely or overexpressed polynucleotide is identified by the method comprising:

(a) obtaining a set of polynucleotides representing gene expression in a target cell;

(b) obtaining a set of polynucleotides representing gene expression in a control cell;

(c) identifying a unique or overexpressed polynucleotide in the target cell as compared to the control cell; and

(d) identifying a unique or overexpressed polynucleotide which is capable of eliciting an immune response in the subject.

19. The method of claim 17, further comprising administering an effective amount of a cytokine and/or co-stimulatory molecule to the subject.

20. The method of claim 17, wherein said immune effector cell is a cytotoxic T lymphocyte.

17. A method for enhancing an immune response in a subject against a target cell, comprising administering to the subject an effective amount of an immune effector cell that was raised against an antigenic peptide that is uniquely expressed or overexpressed in the target cell and has not been previously identified as having the ability to induce an immune response in the subject, whereby an immune response is mounted against the target cell.

21. A method for enhancing an immune response in a subject against a target cell, comprising administering to the subject an effective amount of an antibody that was raised against an antigenic peptide that is uniquely expressed or overexpressed in the target cell and has not been previously identified as having the ability to induce an immune response in the subject, whereby an immune response is mounted against the target cell.

22. The method of claim 21, wherein the uniquely or overexpressed polynucleotide is identified by the method comprising:

(a) obtaining a set of polynucleotides representing gene expression in a target cell;

(b) obtaining a set of polynucleotides representing gene expression in a control cell;

(c) identifying a unique or overexpressed polynucleotide in the target cell as compared to the control cell; and

(d) identifying a unique or overexpressed polynucleotide which is capable of eliciting an immune response in the subject.

23. The method of claim 21, further comprising administering an effective amount of a cytokine and/or co-stimulatory molecule to the subject.

24. The method of claim 21, wherein said antibody is a monoclonal antibody.