MAGE-3 peptides presented by HLA class ll molecules
AssigneesLudwig Institute for Cancer Research, Vrije Universiteit Brussel
InventorsPascal Chaux, Vincent Stroobant, Thierry Boon-Falleur, Pierre van der Bruggen, Kris Thielemans, Jurgen Corthals
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Abstract
The invention describes HLA class II binding peptides encoded by the MAGE-3 tumor associated gene, as well as nucleic acids encoding such peptides and antibodies relating thereto. The peptides stimulate the activity and proliferation of CD4+T lymphocytes. Methods and products also are provided for diagnosing and treating conditions characterized by expression of the MAGE-3 gene.
Claims76
An isolated MAGE-3 HLA class II-binding peptide comprising a fragment of the amino acid sequence of SEQ ID NO:2 which binds an HLA class II molecule, or a functional variant thereof comprising one or more amino acid additions, substitutions or deletions.
A composition comprising an isolated MAGE-3 HLA class I-binding peptide and an isolated MAGE-3 HLA class II-binding peptide.
A method for enriching selectively a population of T lymphocytes with CD4+ T lymphocytes specific for a MAGE-3 HLA class II-binding peptide comprising:
- contacting an isolated population of T lymphocytes with an agent presenting a complex of the MAGE-3 HLA class II-binding peptide and an HLA class II molecule in an amount sufficient to selectively enrich the isolated population of T lymphocytes with the CD4+ T lymphocytes.
25B. The method of claim 24 or 25 wherein the HLA class II molecule is an HLA-DRB1/13 molecule and wherein the MAGE-3 HLA class II-binding peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:11, SEQ ID NO:41 and SEQ ID NO:42.
A method for diagnosing a disorder characterized by expression of MAGE-3 comprising:
- contacting a biological sample isolated from a subject with an agent that is specific for the MAGE-3 HLA class II binding peptide, and
- determining the interaction between the agent and the MAGE-3 HLA class II binding peptide as a determination of the disorder.
A method for diagnosing a disorder characterized by expression of a MAGE-3 HLA class II-binding peptide which forms a complex with an HLA class II molecule, comprising:
- contacting a biological sample isolated from a subject 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 treating a subject having a disorder characterized by expression of MAGE-3, comprising:
- administering to the subject an amount of a MAGE-3 HLA class II-binding peptide sufficient to ameliorate the disorder.
A method for treating a subject having a disorder characterized by expression of MAGE-3, comprising:
- administering to the subject an amount of a MAGE-3 HLA class I-binding peptide and an amount of a MAGE-3 HLA class II-binding peptide sufficient to ameliorate the disorder.
A method for treating a subject having a disorder characterized by expression of MAGE-3, comprising:
- administering to the subject an amount of an agent which enriches selectively in the subject the presence of complexes of an HLA class II molecule and a MAGE-3 HLA class II-binding peptide, sufficient to ameliorate the disorder.
A method for treating a subject having a disorder characterized by expression of MAGE-3, comprising:
- administering to the subject an amount of autologous CD4+ T lymphocytes sufficient to ameliorate the disorder, wherein the CD4+ T lymphocytes are specific for complexes of an HLA class II molecule and a MAGE-3 HLA class II-binding peptide.
A method for identifying functional variants of a MAGE-3 HLA class II binding peptide, comprising
- selecting a MAGE-3 HLA class II binding peptide, an HLA class II binding molecule which binds the MAGE-3 HLA class II binding peptide, and a T cell which is stimulated by the MAGE-3 HLA class II binding peptide presented by the HLA class II binding molecule;
- mutating a first amino acid residue of the MAGE-3 HLA class II binding peptide to prepare a variant peptide;
- determining the binding of the variant peptide to HLA class II binding molecule and the stimulation of the T cell, wherein binding of the variant peptide to the HLA class II binding molecule and stimulation of the T cell by the variant peptide presented by the HLA class II binding molecule indicates that the variant peptide is a functional variant.
An isolated CD4+ T lymphocyte which selectively binds a complex of an HLA class II molecule and a MAGE-3 HLA class II-binding peptide.
An isolated antigen presenting cell which comprises a complex of an HLA class II molecule and a MAGE-3 HLA class II-binding peptide.
Dependencies are inferred from the claim text.