MAGE antigenic peptides which bind HLA-B35 and HLA-B44
OwnerRosalie Luiten, Thierry Boon-Falleur +4inventors
InventorsRosalie Luiten, Thierry Boon-Falleur, Pierre Van der Bruggen, Vincent Stroobant, Nathalie Demotte, Erwin Schultz
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Abstract
The invention provides antigenic peptides derived from MAGE-A1 polypeptides and presented by HLA-B35 and HLA-B44 molecules. Antigenic peptides derived from MAGE-A3 polypeptides and presented by HLA-B35 molecules also are provided. Methods for diagnosis and treatment which involve the polypeptides also are provided.
Claims78
A method for diagnosing a disorder characterized by expression of MAGE-A 1 in a subject typed as HLA-B35 positive, comprising:
- contacting a biological sample isolated from the subject with an agent that is specific for a MAGE-A1 HLA binding peptide which comprises SEQ ID NO:10, and
- determining the interaction between the agent and the MAGE-A1 HLA binding peptide as a determination of the disorder.
A method for diagnosing a disorder characterized by expression of MAGE-A1 in a subject typed as HLA-B44 positive, comprising:
- contacting a biological sample isolated from the subject with an agent that is specific for a MAGE-A1 HLA binding peptide which comprises SEQ ID NO:53, and
- determining the interaction between the agent and the MAGE-A1 HLA binding peptide as a determination of the disorder.
A method for diagnosing a disorder characterized by expression of a complex of a MAGE-A1 HLA-B35 or HLA-B44 binding peptide and a HLA-B35 or HLA-B44 molecule, comprising:
- contacting a biological sample isolated from a subject suspected of having the disorder with an agent that binds the complex;
- and
- determining binding between the complex and the agent as a determination of the disorder.
A method for enriching selectively a population of T lymphocytes with T lymphocytes specific for a MAGE-A1 HLA binding peptide, comprising:
- contacting a source of T lymphocytes which contains a population of T lymphocytes with an agent presenting a complex of a MAGE-A1 HLA-B35 binding peptide comprising SEQ ID NO:10 and a HLA-B35 molecule or a complex of a MAGE-A1 HLA-B44 binding peptide comprising SEQ ID NO:53 and a HLA-B44 molecule, in an amount sufficient to selectively enrich the population of T lymphocytes with the T lymphocytes specific for one of the complexes.
A method for treating a subject, typed as HLA-B35 or HLA-B44 positive, having a disorder characterized by expression of MAGE-A1, comprising:
- administering to the subject an amount of a MAGE-A1 HLA-B35 binding peptide comprising SEQ ID NO:10or a MAGE-A1 HLA-B44 binding peptide comprising SEQ ID NO:53 sufficient to ameliorate the disorder.
A method for treating a subject, typed as HLA-B35 or HLA-B44 positive, having a disorder characterized by expression of MAGE-A1, comprising:
- administering to the subject an amount of an agent which enriches selectively in the subject the presence of complexes of a HLA-B35 molecule and a MAGE-A1 HLA-B35 binding peptide comprising SEQ ID NO:10, or a HLA-B44 molecule and a MAGE-A1 HLA-B44 binding peptide comprising SEQ ID NO:53, in an amount sufficient to ameliorate the disorder.
A method for treating a subject, typed as HLA-B35 or HLA-B44 positive, having a disorder characterized by expression of MAGE-A1, comprising:
- administering to the subject an amount of autologous T lymphocytes sufficient to ameliorate the disorder, wherein the T lymphocytes are specific for complexes of a HLA-B35 molecule and a MAGE-A1 HLA-B35 binding peptide comprising SEQ ID NO:10, or a HLA-B44 molecule and a MAGE-A1 HLA-B44 binding peptide comprising SEQ ID NO:53.
A method for identifying functional variants of a MAGE-A1 HLA-B35 or HLA-B44 binding peptide, comprising
- providing (1) a MAGE-A1 HLA-B35 binding peptide comprising SEQ ID NO:10, and a HLA-B35 molecule, or (2) a MAGE-A1 HLA-B44 binding peptide comprising SEQ ID NO:53, and a HLA-B44 molecule, and a T cell which is stimulated by the MAGE-A1 HLA binding peptide presented by the HLA-B35 or HLA-B44 molecule;
- mutating a first amino acid residue of the MAGE-A1 HLA-B35 or HLA-B44 binding peptide to prepare a variant peptide;
- and
- determining the binding of the variant peptide to the HLA-B35 or HLA-B44 molecule or the stimulation of the T cell, wherein binding of the variant peptide to the HLA binding molecule or stimulation of the T cell by the variant peptide presented by the HLA binding molecule indicates that the variant peptide is a functional variant.
An expression vector comprising a nucleotide sequence which encodes an amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10, operably linked to a promoter, and a nucleotide sequence which encodes the amino acid sequence of a HLA-B*35 molecule, operably linked to a promoter.
An expression vector comprising a nucleotide sequence which encodes an amino acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:14 and SEQ ID NO:53, operably linked to a promoter, and a nucleotide sequence which encodes the amino acid sequence of a HLA-B*44 molecule operably linked to a promoter.
An isolated T lymphocyte which selectively binds a complex of a HLA-B35 molecule and a MAGE-A1 HLA binding peptide which comprises the amino acid sequence of SEQ ID NO:10.
An isolated T lymphocyte which selectively binds a complex of a HLA-B44 molecule and a MAGE-A1 HLA binding peptide which comprises the amino acid sequence of SEQ ID NO:53.
An isolated antigen presenting cell which comprises a complex of a HLA-B35 molecule and a MAGE-A1 HLA binding peptide which comprises the amino acid sequence of SEQ ID NO:10.
An isolated antigen presenting cell which comprises a complex of a HLA-B44 molecule and a MAGE-A1 HLA binding peptide which comprises the amino acid sequence of SEQ ID NO:53.
A method for identifying a candidate mimetic of a MAGE-A1 HLA-B35 or HLA-B44 binding peptide, comprising
- providing a HLA-B35 or HLA-B44 molecule,
- contacting the HLA molecule with a test molecule, and
- determining the binding of the test molecule to the HLA molecule, wherein a test molecule which binds to the HLA molecule is a candidate mimetic of the MAGE-A1 HLA binding peptide.
A method for diagnosing a disorder characterized by expression of MAGE-A3 in a subject typed as HLA-B35 positive, comprising:
- contacting a biological sample isolated from the subject with an agent that is specific for a MAGE-A3 HLA binding peptide which comprises SEQ ID NO:56, and
- determining the interaction between the agent and the MAGE-A3 HLA binding peptide as a determination of the disorder.
A method for diagnosing a disorder characterized by expression of a complex of a MAGE-A3 HLA-B35 binding peptide and a HLA-B35 molecule, comprising:
- contacting a biological sample isolated from a subject suspected of having the disorder with an agent that binds the complex;
- and
- determining binding between the complex and the agent as a determination of the disorder.
A method for enriching selectively a population of T lymphocytes with T lymphocytes specific for a MAGE-A3 HLA binding peptide, comprising:
- contacting a source of T lymphocytes which contains a population of T lymphocytes with an agent presenting a complex of a MAGE-A3 HLA-B35 binding peptide comprising SEQ ID NO:56 and a HLA-B35 molecule, in an amount sufficient to selectively enrich the population of T lymphocytes with the T lymphocytes specific for one of the complexes.
A method for treating a subject, typed as HLA-B35 positive, having a disorder characterized by expression of MAGE-A3, comprising:
- administering to the subject an amount of a MAGE-A3 HLA-B35 binding peptide comprising SEQ ID NO:56 sufficient to ameliorate the disorder.
A method for treating a subject, typed as HLA-B35 positive, having a disorder characterized by expression of MAGE-A3, comprising:
- administering to the subject an amount of an agent which enriches selectively in the subject the presence of complexes of a HLA-B35 molecule and a MAGE-A3 HLA-B35 binding peptide comprising SEQ ID NO:56, in an amount sufficient to ameliorate the disorder.
A method for treating a subject, typed as HLA-B35 positive, having a disorder characterized by expression of MAGE-A3, comprising:
- administering to the subject an amount of autologous T lymphocytes sufficient to ameliorate the disorder, wherein the T lymphocytes are specific for complexes of a HLA-B35 molecule and a MAGE-A3 HLA-B35 binding peptide comprising SEQ ID NO:56.
A method for identifying functional variants of a MAGE-A3 HLA-B35 binding peptide, comprising providing a MAGE-A3 HLA-B35 binding peptide comprising SEQ ID NO:56, a HLA-B35 molecule, and a T cell which is stimulated by the MAGE-A3 HLA binding peptide presented by the HLA-B35 molecule;
- mutating a first amino acid residue of the MAGE-A3 HLA-B35 binding peptide to prepare a variant peptide;
- and
- determining the binding of the variant peptide to the HLA-B35 molecule or the stimulation of the T cell, wherein binding of the variant peptide to the HLA binding molecule or stimulation of the T cell by the variant peptide presented by the HLA binding molecule indicates that the variant peptide is a functional variant.
An expression vector comprising a nucleotide sequence which encodes an amino acid sequence selected from the group consisting of SEQ ID NO:56, SEQ ID NO:57 and SEQ ID NO:59, operably linked to a promoter, and a nucleotide sequence which encodes the amino acid sequence of a HLA-B35 molecule, operably linked to a promoter.
An isolated T lymphocyte which selectively binds a complex of a HLA-B35 molecule and a MAGE-A3 HLA binding peptide which comprises the amino acid sequence of SEQ ID NO:56.
An isolated antigen presenting cell which comprises a complex of a HLA-B35 molecule and a MAGE-A3 HLA binding peptide which comprises the amino acid sequence of SEQ ID NO:56.
A method for identifying a candidate mimetic of a MAGE-A3 HLA-B35 binding peptide, comprising
- providing a HLA-B35 molecule,
- contacting the HLA molecule with a test molecule, and
- determining the binding of the test molecule to the HLA molecule, wherein a test molecule which binds to the HLA molecule is a candidate mimetic of the MAGE-A3 HLA binding peptide.
Dependencies are inferred from the claim text.