Tumor-associated peptides binding promiscuously to human leukocyte antigen (HLA) class II molecules

• US 7,833,969 B2
• Filed: 11/19/2007
• Issued: 11/16/2010
• 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
• Primary Examiner(s): Tate; Christopher R.
• Assistant Examiner(s): TELLER, ROY R
• Application Number:
  US11/942,598
• Publication Number:
  US 20080206217A1
• Time in Patent Office: 1,093 Days
• Field of Search: None
• US Class Current: 514/19.3
• 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 tumor-associated T-helper cell peptide epitopes, alone or in combination with other tumor-associated peptides, that serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumor immune responses. In particular, the present invention relates to 49 novel peptide sequences derived from HLA class II molecules of human tumor cell lines which can be used in vaccine compositions for eliciting anti-tumor immune responses.

Claims

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

4 flanked by N- and/or C-terminal extensions from 1 to 10 amino acids in length.

2. The isolated tumour associated peptide according to claim 1 wherein said isolated tumor associated 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. A pharmaceutical composition comprising the tumour associated peptide of claim 1 and a pharmaceutically acceptable carrier.

5. 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.

6. 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.

7. Activated cytotoxic T lymphocytes (CTL), produced by the method of claim 6, wherein the CTL selectively recognise a cell that aberrantly expresses a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:

4.

3. A fusion protein comprising a peptide set forth in SEQ ID NO:

4, and N-terminal amino acids of HLA-DR antigen-associated invariant chain (Ii).

8. A pharmaceutical composition comprising a fusion protein of claim 3 and a pharmaceutically acceptable carrier.

9. An isolated tumour associated peptide consisting of the peptide set forth in SEQ ID NO:

4.