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Hla-dr-binding antigen peptide derived from wt1Hla-dr-binding antigen peptide derived from wt1 description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20080070835, Hla-dr-binding antigen peptide derived from wt1. Brief Patent Description - Full Patent Description - Patent Application Claims
TECHNICAL FIELD [0001]The present invention relates to HLA-DRB1*0405-binding antigen peptides derived from WT1. BACKGROUND ART [0002]WT1 gene (Wilms' tumor gene 1) has been identified as one of causative genes of Wilms' tumor that is a childhood renal tumor (Cell 60: 509, 1990, Nature 343: 774, 1990). WT1 gene encodes the transcription factor WT1 which plays an important role in many processes such as proliferation, differentiation and apoptosis of cells, and development of tissues (Int. Rev. Cytol. 181: 151, 1998). WT1 gene was originally defined as a tumor suppressor gene. However, subsequent studies revealed that WT1 gene is highly expressed in leukemia and various solid cancers including lung cancer and breast cancer, indicating that WT1 gene rather exerts an oncogenic function that promotes cancer growth. In addition, it was demonstrated that, when peripheral blood mononuclear cells positive for HLA-A*0201 or HLA-A*2402 were stimulated in vitro with WT1-derived peptides, peptide-specific cytotoxic T-lymphocytes (CTLs) were induced and killed leukemic or solid tumor cells which endogenously express WT1. These results demonstrated that WT1 is a promising target molecule of cancer immunotherapy (Int. J. Hematol 76: 127, 2002). [0003]It has been reported that presence of helper T cells specific to cancer antigen is essential for effective induction of CTLs (Cancer. Res. 62: 6438, 2002). [0004]Helper T cells (CD4-positive T cells) are induced (made proliferate) and activated when they recognize a complex of MHC class II molecule and antigen peptide on antigen-presenting cells. The activated helper T cells produce cytokines such as IL-2, IL-4, IL-5, IL-6, and/or interferons and mediate the growth, differentiation, and maturation of B cells. The activated helper T cells also function to promote the growth, differentiation or maturation of other subsets of T cells such as Tc and TD cells. Thus, the activated helper T cells can activate the immune system through the promotion of growth and activation of B and T cells. Therefore, it was suggested to be helpful to enhance functions of helper T cells being under the influence of MHC-class II-binding antigen peptide (also referred to as "helper peptide"), whereby efficacy (potency) of cancer vaccine in cancer immunotherapy (cancer vaccine therapy) is increased (J. Immunother., 24:195, 2001). [0005]As for WT1-derived peptides, only one antigen peptide is known to bind to a subtype of MHC class II molecule, i.e., HLA-DRB1*0401 (Cancer Immunol. Immunother. 51:271, 2002). There are no WT1-derived peptides which have been reported to bind to different subtypes. DISCLOSURE OF INVENTION [0006]The purpose of the present invention is to provide HLA-DRB1*0405-binding antigen peptides derived from WT1, and use of the peptide as an enhancer of cancer vaccine efficacy (an agent for enhancing efficacy of cancer vaccine). [0007]The present inventor has conducted intensive study on WT1-derived antigen peptides ("helper peptides") having an activity of binding to MHC class II antigen and enhancing the cancer vaccine efficacy (potency) in cancer immunotherapy. In consequence, the present inventor has for the first time found that WT1 contains an antigen peptide portion(s) which has an activity of binding to HLA-DRB1*0405 among a number of MHC class II subclasses and inducing helper T cells. This finding led to the development of a novel therapeutic method by which WT1-specific helper T cells are induced and enhanced in HLA-DRB1*0405-positive cancer patients. [0008]Recent researches revealed that there exists promiscuous helper peptides which are helper peptides capable of binding to plural HLA-class II molecules and inducing helper CD4-positive T cells (British J cancer, 85(10), p1527-1534 (2001); J. Immunol., 169, p557-565 (2002)). The present inventor made investigation into WT1.sub.332-347, which is one of the above-described HLA-DRB1*0405-binding antigen peptides (helper peptides), to elucidate whether or not it is potentially a promiscuous helper peptide. As a result, said peptide proved to be a promiscuous helper peptide that binds not only to HLA-DRB1*0405 molecule but also to HLA-DRB1*1502. Thus, the WT1.sub.332-347 peptide of the present invention is a helper peptide applicable to patients having HLA-DRB1*1502 as well as those having HLA-DRB1*0405. The present inventor also found that WT1 contains an antigen peptide portion(s) capable of binding to HLA-DRB1*1502, one of a number of MHC class II subclasses, and inducing helper T cells for the first time. [0009]The present invention has been established on the basis of these findings. [0010]The present invention encompasses the followings. [0011](1) A peptide consisting of 10-25 contiguous amino acids in the amino acid sequence of human WT1 shown in SEQ ID NO: 1, which binds to HLA-DRB1*0405 and induces helper T cells. [0012](2) The peptide of (1) above, which comprises an amino acid sequence set forth in any one of SEQ ID NOS: 2-23. [0013](3) The peptide of (2) above, which comprises the amino acid sequence set forth in SEQ ID NO: 24. [0014](4) A peptide of 10-25 amino acids, which comprises an amino acid sequence wherein the amino acid residue at position 1, 4, 6 and/or 9 of an amino acid sequence set forth in any one of SEQ ID NOS: 2-23 is substituted by another amino acid residue, and which binds to an HLA-DRB1*0405 and induces helper T cells. [0015](5) The peptide of (4) above, which comprises an amino acid sequence wherein the amino acid residue at position 1, 4, 6 and/or 9 of an amino acid sequence set forth in any one of SEQ ID NOS: 2-23 is substituted by an amino acid residue selected from the following amino acids: [0016]phenylalanine, tyrosine, tryptophan, valine, isoleucine, leucine and methionine for the position 1; [0017]valine, isoleucine, leucine, methionine, aspartic acid and glutamic acid for the position 4; [0018]asparagine, serine, threonine, glutamine, lysine and aspartic acid for the position 6; and [0019]aspartic acid, glutamic acid and glutamine for the position 9. [0020](6) The peptide of (5) above, which comprises an amino acid sequence wherein the amino acid residue at position 3, 6, 8 and/or 11 of the amino acid sequence set forth in SEQ ID NO: 24 is substituted by an amino acid residue selected from the following amino acids: [0021]phenylalanine, tryptophan, valine, isoleucine, leucine and methionine for the position 3; [0022]valine, isoleucine, methionine, aspartic acid and glutamic acid for the position 6; [0023]asparagine, serine, threonine, glutamine, lysine and aspartic acid for the position 8; and [0024]aspartic acid, glutamic acid and glutamine for the position 11. [0025](7) A peptide consisting of 10-25 contiguous amino acids in the amino acid sequence of human WT1 shown in SEQ ID NO: 1, which binds to HLA-DRB1*1502 and induces helper T cells. [0026](8) The peptide of (7) above, which comprises an amino acid sequence set forth in any one of SEQ ID NOS: 46-56. [0027](9) The peptide of (7) above, which comprises the amino acid sequence set forth in SEQ ID NO: 24. [0028](10) A peptide comprising a peptide described in any one of (1) to (9) above together with a cancer antigen peptide. [0029](11) A polynucleotide encoding a peptide described in any one of (1) to (10) above. Continue reading about Hla-dr-binding antigen peptide derived from wt1... Full patent description for Hla-dr-binding antigen peptide derived from wt1 Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Hla-dr-binding antigen peptide derived from wt1 patent application. Patent Applications in related categories: 20090291893 - Compositions for the prevention and treatment of neuroinjury and methods of use thereof - A method for preventing or ameliorating secondary neuronal injury and inflammation following traumatic brain injury (TBI) is disclosed. 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