WT1 HLA class II—binding peptides and compositions and methods comprising same
US-9233149-B2 · Jan 12, 2016 · US
US10654892B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10654892-B2 |
| Application number | US-201113877768-A |
| Country | US |
| Kind code | B2 |
| Filing date | Oct 4, 2011 |
| Priority date | Oct 5, 2010 |
| Publication date | May 19, 2020 |
| Grant date | May 19, 2020 |
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The present invention relates to a method for activating helper T cells, which includes the step of activating helper T cells by adding a WT1 peptide to antigen presenting cells, wherein the WT1 peptide has the ability to bind to any MHC class II molecule of an HLA-DRB1*0101 molecule, an HLA-DRB1*0401 molecule, an HLA-DRB1*0403 molecule, an HLA-DRB1*0406 molecule, an HLA-DRB1*0803 molecule, an HLA-DRB1*0901 molecule, an HLA-DRB1*1101 molecule, an HLA-DRB3*0202 molecule, an HLA-DRB4*0101 molecule, an HLA-DPB1*0201 molecule or an HLA-DPB1*0301 molecule, and the like.
Opening claim text (preview).
The invention claimed is: 1. A method for producing an activated helper T cell, comprising: contacting a WT1 peptide with an antigen-presenting cell comprising one or two MHC class II molecules selected from the group consisting of an HLA-DRB1*0403 molecule, an HLA-DRB1*0406 molecule, an HLA-DRB1*0803 molecule, an HLA-DRB3*0202 molecule, an HLA-DRB4*0101 molecule, an HLA-DPB1*0201 molecule, and an HLA-DPB1*0301 molecule, wherein the WT1 peptide consists of the amino acid sequence of SEQ ID NO: 2 and is capable of binding to the one or two MHC class II molecules. 2. The method of claim 1 , wherein the antigen-presenting cell comprises two of the MHC class II molecules. 3. The method of claim 1 , wherein the antigen-presenting cell further comprises an HLA-DRB1*0405 molecule, an HLA-DRB1*1501 molecule, an HLA-DRB1*1502 molecule, an HLA-DPB1*0501 molecule, an HLA-DPB1*0901 molecule, or a combination thereof, to which the WT1 peptide is capable of binding. 4. The method of claim 1 , wherein the WT1 peptide is modified by esterification, alkylation, halogenation, or phosphorylation of a functional group in a side chain of an amino acid residue of the WT1 peptide, or addition of a histidine tag or a detectable label to the WT1 peptide. 5. The method of claim 1 , wherein the antigen-presenting cell is an isolated dendritic cell. 6. The method of claim 1 , wherein the antigen-presenting cell is an isolated peripheral blood mononuclear cell. 7. A method for producing an activated helper T cell, comprising: contacting a WT1 peptide with an antigen-presenting cell comprising at least one of an isolated dendritic cell and an isolated peripheral blood mononuclear cell, and comprising one or two MHC class II molecules selected from the group consisting of an HLA-DRB1*0403 molecule, an HLA-DRB1*0406 molecule, an HLA-DRB1*0803 molecule, an HLA-DRB3*0202 molecule, an HLA-DRB4*0101 molecule, an HLA-DPB1*0201 molecule, and an HLA-DPB1*0301 molecule, wherein the WT1 peptide consists of the amino acid sequence of SEQ ID NO: 2 and is capable of binding to the one or two MHC class II molecules. 8. The method of claim 7 , wherein the antigen-presenting cell is an isolated dendritic cell. 9. The method of claim 7 , wherein the antigen-presenting cell is an isolated peripheral blood mononuclear cell. 10. A method for producing an activated helper T cell in vivo, comprising: administering a WT1 peptide to a subject having an antigen-presenting cell such that the WT1 peptide is contacted with the antigen-presenting cell in vivo, wherein the antigen-presenting cell comprises one or two MHC class II molecules selected from the group consisting of an HLA-DRB1*0403 molecule, an HLA-DRB1*0406 molecule, an HLA-DRB1*0803 molecule, an HLA-DRB3*0202 molecule, an HLA-DRB4*0101 molecule, an HLA-DPB1*0201 molecule, and an HLA-DPB1*0301 molecule, and the WT1 peptide consists of the amino acid sequence of SEQ ID NO: 2 and is capable of binding to the one or two MHC class II molecules. 11. The method of claim 1 , wherein the activated helper T cell is produced in vitro. 12. A method for activating a helper T cell in a subject requiring the activation, comprising: administering a WT1 peptide to the subject who has one or two MHC class II molecules selected from the group consisting of an HLA-DRB1*0101 molecule, an HLA-DRB1*0401 molecule, an HLA-DRB1*0403 molecule, an HLA-DRB1*0406 molecule, an HLA-DRB1*0803 molecule, an HLA-DRB1*0901 molecule, an HLA-DRB1*1101 molecule, an HLA-DRB3*0202 molecule, an HLA-DRB4*0101 molecule, an HLA-DPB1*0201 molecule, and an HLA-DPB1*0301 molecule, wherein the WT1 peptide is capable of binding to the one or two MHC class II molecules, and consists of the amino acid sequence of SEQ ID NO: 2, and the subject has cancer cells endogenously expressing the Wilms' tumor 1 gene (WT1). 13. A method, comprising: administering a WT1 peptide to a subject who has been diagnosed with cancer and has an MHC class II molecule selected from the group consisting of an HLA-DRB1*0101 molecule, an HLA-DRB1*0401 molecule, an HLA-DRB1*0403 molecule, an HLA-DRB1*0406 molecule, an HLA-DRB1*0803 molecule, an HLA-DRB1*0901 molecule, an HLA-DRB1*1101 molecule, an HLA-DRB3*0202 molecule, an HLA-DRB4*0101 molecule, an HLA-DPB1*0201 molecule, and an HLA-DPB1*0301 molecule, wherein the WT1 peptide consists of the amino acid sequence of SEQ ID NO: 2 and is capable of binding to the MHC class II molecule, and the cancer cells endogenously express the Wilms' tumor 1 gene (WT1). 14. The method of claim 1 , wherein the antigen-presenting cell comprises one of the MHC class II molecules. 15. The method of claim 3 , wherein the WT1 peptide is modified by esterification, alkylation, halogenation, or phosphorylation of a functional group in a side chain of an amino acid residue of the WT1 peptide, or addition of a histidine tag or a detectable label to the WT1 peptide. 16. The method of claim 3 , wherein the antigen-presenting cell is an isolated dendritic cell. 17. The method of claim 3 , wherein the antigen-presenting cell is an isolated peripheral blood mononuclear cell. 18. The method of claim 3 , wherein the activated helper T cell is produced in vitro. 19. The method of claim 15 , wherein the antigen-presenting cell is an isolated dendritic cell. 20. The method of claim 15 , wherein the antigen-presenting cell is an isolated peripheral blood mononuclear cell.
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