Method for treating subjects by using BAGE tumor rejection antigen precursors or tumor rejection antigens

• US 6,638,512 B1
• Filed: 08/25/1999
• Issued: 10/28/2003
• Est. Priority Date: 06/17/1993
• Status: Expired due to Fees

• Current Assignee: Ludwig Institute for Cancer Research, Ltd.
• Original Assignee: Ludwig Institute for Cancer Research, Ltd.
• Inventors: Bo{haeck over (e)}l, Pascale, Renauld, Jean-Christophe, Boon-Falleur, Thierry, Coulie, Pierre, van der Bruggen, Pierre, Wildmann, Claude
• Primary Examiner(s): SAUNDERS, DAVID A
• Application Number:
  US09/382,497
• Time in Patent Office: 1,525 Days
• Field of Search: 424/93.71, 424/193.1, 424/271.1, 424/93.7, 424/573, 424/93.21, 424/185.1, 424/277.1
• US Class Current: 424/185.1
• 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: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
• CPC Class Codes: C07K 14/70539 MHC-molecules, e.g. HLA-molecules

Abstract

A family of tumor rejection antigen precursors, and the nucleic acid molecules which code for them, are disclosed. These tumor rejection antigen precursors are referred to as BAGE tumor rejection antigen precursors, and the nucleic acid molecules which code for them are referred to as BAGE coding molecules. Various diagnostic and therapeutic uses of the coding sequences and the tumor rejection antigen precursor molecules are described.

Claims

1. A method for treating a subject with a disorder characterized by the presence of complexes of HLA molecules and the peptide of SEQ ID NO:

3 on cell surfaces, comprising administering to said subject an amount of cytolytic T cells specific to complexes of HLA molecules and said peptide, sufficient to alleviate said disorder.

2. A method for treating a subject with a disorder characterized by expression of a BAGE tumor rejection antigen precursor which is processed to a tumor rejection antigen presented by HLA-C molecules, said method comprising:

administering to said subject a composition comprising cytolytic T cells specific to complexes of said BAGE tumor rejection antigen and HLA-C molecules in an amount sufficient to lyse cells presenting said complexes and alleviate said disorder, wherein the BAGE tumor rejection antigen consists of the amino acid sequence of SEQ ID NO;

3.

3. The method of claim 2, wherein the HLA-C molecule is HLA-Cw*1601.

4. A method for treating a subject with a disorder characterized by expression of a BAGE tumor rejection antigen precursor (TRAP) which is processed to a BAGE tumor rejection antigen (TRA) presented by HLA-C molecules, said method comprising:

administering to said subject a composition comprising an amount of the isolated BAGE TRAP which provokes an immune response to complexes of the HLA-C and the TRA, and which is sufficient to provoke said immune response against cells presenting the complexes, wherein the BAGE TRAP comprises the amino acid sequence of SEQ ID NO;

2.

5. The method of claim 4, wherein the composition further comprises a cell transformed or transfected with a nucleic acid molecule that encodes the HLA-C molecule.

6. The method of claim 5, wherein the HLA-C molecule is HLA-Cw*1601.

7. A method for treating a subject with a disorder characterized by expression of a BAGE TRAP which is processed to a BAGE TRA presented by HLA-C molecules, said method comprising:

administering to said subject a composition comprising cells transformed or transfected with a nucleic acid molecule that encodes the TRAP, wherein the cell expresses HLA-C on the cell surface and wherein the nucleic acid molecule that encodes the TRAP comprises the nucleotide sequence encoding the polypeptide of SEQ ID NO;

2, and wherein said cells present complexes of HLA-C and TRA on their surfaces and wherein said composition is administered in an amount sufficient to provoke an immune response against cells presenting the complexes.

8. The method of claim 7, wherein the HLA-C molecule is HLA-Cw*1601.

9. The method of claim 7, wherein the nucleic acid molecule that encodes the TRAP comprises the nucleotide sequence of SEQ ID NO:

1.

10. A method for treating a subject with a disorder characterized by expression of a BAGE TRAP which is processed to a BAGE TRA presented by HLA-Cw*1601 molecules comprising;

administering to said subject a composition comprising an amount of cells transformed or transfected with a nucleic acid molecule that encodes the HLA-C molecule and a nucleic acid molecule that encodes the TRAP, and wherein the nucleic acid molecule that encodes the TRAP comprises the nucleotide sequence encoding the polypeptide of SEQ ID NO;

2, and wherein said cells present complexes of HLA-Cw*1601 and TRA on their surfaces and wherein said composition is administered in an amount sufficient to provoke an immune response against cells presenting the complexes.

11. The method of claim 10, wherein the cell is transformed or transfected with a nucleic acid molecule that encodes both the HLA-Cw*1601 molecule and the TRAP.

12. The method of claim 10, wherein the nucleic acid molecule that encodes the TRAP comprises the nucleotide sequence of SEQ ID NO:

1.

13. A method for treating a subject with a disorder characterized by expression of a BAGE TRAP which is processed to a BAGE TRA which is presented by HLA-C molecules and wherein said BAGE TRA consists of the amino acid sequence of SEQ ID NO:

3, said method comprising;

administering to said subject a composition comprising cells transformed or transfected with a nucleic acid molecule that encodes the BAGE TRA consisting of the amino acid sequence of SEQ ID NO;

3, wherein the cell expresses HLA-C molecules on the cell surface, and wherein said cells present complexes of HLA-C molecules and the BAGE TRA on their surfaces and wherein said composition is administered in an amount sufficient to provoke an immune response against cells presenting the complexes.

14. The method of claim 13, wherein the HLA-C molecule HLA-Cw*1601.

15. A method for treating a subject with a disorder characterized by expression of a BAGE TRAP which is processed to a BAGE TRA which is presented by HLA-Cw*1601 molecules and wherein said BAGE TRA consists of the amino acid sequence of SEQ ID NO:

3, said method comprising;

administering to said subject a composition comprising an amount of cells transformed or transfected with a nucleic acid molecule that encodes the HLA-C molecule and a nucleic acid molecule that encodes the BAGE TRA consisting of the amino acid sequence of SEQ ID NO;

3, and wherein said cells present complexes of HLA-Cw*1601 molecules and the TRA on their surfaces and wherein said composition is administered in an amount sufficient to provoke an immune response against cells presenting the complexes.

16. The method of claim 15, wherein the cell is transformed or transfected with a nucleic acid molecule that encodes both the HLA-C molecule and the BAGE TRA.

17. A method for treating a subject with a disorder characterized by expression of a BAGE tumor rejection antigen precursor (TRAP) which is processed to a BAGE tumor rejection antigen (TRA) which is presented by HLA-C molecules and wherein said TRA consists of the amino acid sequence of SEQ ID NO:

3, said method consisting of administering to said subject a composition wherein the immunogenic component consists of an amount of the TRA consisting of the amino acid sequence of SEQ ID NO;

3 which provokes an immune response to complexes of HLA-C molecules and the TRA, and which is sufficient to provoke said immune response against cells presenting the complexes.

18. A method for treating a subject with a disorder characterized by expression of a BAGE tumor rejection antigen precursor (TRAP) which is processed to a BAGE tumor rejection antigen (TRA) which is presented by HLA-C molecules and wherein said TRA consists of the amino acid sequence of SEQ ID NO:

3, said method consisting of;

administering to said subject a composition consisting of (i) an amount of the TRA consisting of the amino acid sequence of SEQ ID NO;

3 which provokes an immune response to complexes of HLA-C molecules and the TRA, and which is sufficient to provoke said immune response against cells presenting the complexes and (ii) an HLA-C molecule.

19. The method of claim 18, wherein the HLA-C molecule is HLA-Cw*1601.

20. A method for treating a subject with a disorder characterized by expression of a BAGE tumor rejection antigen precursor (TRAP) which is processed to a BAGE tumor rejection antigen (TRA) which is presented by HLA-C molecules and wherein said TRA consists of the amino acid sequence of SEQ ID NO:

3, said method comprising;

administering to said subject a composition comprising (i) an amount of the TRA consisting of the amino acid sequence of SEQ ID NO;

3 which provokes an immune response to complexes of HLA-C molecules and the TRA, and which is sufficient to provoke said immune response against cells presenting the complexes and (ii) a cell transformed or transfected with a nucleic acid molecule that encodes the HLA-C molecule.

21. The method of claim 20, wherein the HLA-C molecule is HLA-CW* 1601.