Tumor-associated Peptides Binding Promiscuously to Human Leukocyte Antigen (HLA) Class II Molecules

• US 20080206217A1
• Filed: 11/19/2007
• Published: 08/28/2008
• Est. Priority Date: 09/05/2005
• Status: Active Grant

• Current Assignee: Immatics Biotechnologies GmbH (Immatics NV)
• Original Assignee: Immatics Biotechnologies GmbH (Immatics NV)
• Inventors: Dengjel, Jorn
• Granted Patent: US 7,833,969 B2
• Time in Patent Office: Days
• US Class Current: 424/93.71
• 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: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex

Abstract

The present invention relates to immunotherapeutic methods, and molecules and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumour-associated T-helper cell peptide epitopes, alone or in combination with other tumour-associated peptides, that serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumour immune responses. In particular, the present invention relates to 49 novel peptide sequences derived from HLA class II molecules of human tumour cell lines which can be used in vaccine compositions for eliciting anti-tumour immune responses.

Claims

1. An isolated tumour associated peptide comprising the peptide set forth in SEQ ID NO:

4 provided that the peptide is not an intact human tumour associated polypeptide.

2. The tumour associated peptide according to claim 1 wherein said peptide is between 9 and 30 amino acids in length.

3. The tumour associated peptide according to claim 1 wherein the peptide has the ability to bind human major histocompatibility complex (MHC) class-II molecule HLA-DRB*0101, and has the ability to bind to at least one additional molecule of the human major histocompatibility complex (MHC) class-II.

4. The tumour associated peptide according to claim 1 wherein the peptide is a fusion protein comprising N-terminal amino acids of the HLA-DR antigen-associated invariant chain (Ii).

5. An isolated nucleic acid encoding the peptide of claim 1.

6. An expression vector capable of expressing the nucleic acid according to claim 5.

7. A host cell comprising an expression vector according to claim 6.

8. An isolated host cell comprising the peptide of claim 1.

9. A method of producing the tumour associated peptide according to claim 1, the method comprising:

culturing the host cell according to claim 7 in a culture medium, wherein the host cell is a recombinant RCC or Awelss cell; and

isolating the peptide from the host cell or its culture medium.

10. A pharmaceutical composition comprising the tumour associated peptide of claim 1 and a pharmaceutically acceptable carrier.

11. A pharmaceutical composition comprising the expression vector according to claim 6 and a pharmaceutically acceptable carrier.

12. A method of killing target cells in a patient wherein the target cells aberrantly express a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:

4, the method comprising administering to the patient an effective amount of the peptide of claim 1, wherein the amount of said peptide is effective to provoke an anti-target cell immune response in said patient.

13. A method of killing target cells in a patient wherein the target cells aberrantly express a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:

4, the method comprising administering to the patient an effective amount of the expression vector according to claim 6, wherein the amount of protein expressed is effective to provoke an anti-target cell immune response in said patient.

14. An in vitro method for producing activated cytotoxic T lymphocytes (CTL), the method comprising contacting in vitro CTL with antigen loaded human class II MHC molecules expressed on the surface of a suitable antigen-presenting cell for a period of time sufficient to activate said CTL in an antigen specific manner, wherein said antigen is the peptide of claim 1.

15. Activated cytotoxic T lymphocytes (CTL), produced by the method of claim 14, wherein the CTL selectively recognise a cell that aberrantly expresses a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:

4.

16. A T-cell receptor (TCR) that recognises a cell that aberrantly expresses a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:

4, the TCR being obtainable from the cytotoxic T lymphocyte (CTL) of claim 15.

17. An isolated nucleic acid encoding the T-cell receptor of claim 15.

18. An expression vector capable of expressing a nucleic acid encoding a T-cell receptor (TCR) according to claim 16.

19. A method of killing target cells in a patient wherein the target cells aberrantly express a polypeptide comprising an amino acid sequence set forth in SEQ ID NO:

4, the method comprising administering to the patient an effective number of the cytotoxic T lymphocytes (CTL) as defined in claim 15.

20. A method of killing target cells in a patient wherein the target cells aberrantly express a polypeptide comprising an amino acid sequence set forth in SEQ ID NO:

4, the method comprising the steps of;

(1) obtaining cytotoxic T lymphocytes (CTL) from the patient;

(2) introducing into said cells the nucleic acid of claim 17; and

(3) introducing the cells produced in step (2) into the patient.