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CN-113321704-B - CDCA 1-derived peptides and vaccines containing the same

CN113321704BCN 113321704 BCN113321704 BCN 113321704BCN-113321704-B

Abstract

The present invention provides CDCA 1-derived epitope peptides having the ability to induce cytotoxic T cells. The invention also provides polynucleotides encoding the peptides, antigen presenting cells presenting the peptides, and cytotoxic T cells targeting the peptides, and methods of inducing antigen presenting cells or CTLs. The invention also provides compositions and pharmaceutical compositions containing them as active ingredients. In addition, the present invention provides methods of treating and/or preventing cancer, and/or preventing postoperative recurrence thereof, using the peptides, polynucleotides, antigen presenting cells, cytotoxic T cells, or pharmaceutical compositions of the present invention. Methods of inducing an immune response against cancer are also provided.

Inventors

  • TSUNODA TAKUYA
  • OHSAWA RYUJI
  • YAMASHITA SHOKO
  • Watari haruhisa

Assignees

  • 肿瘤疗法科学股份有限公司

Dates

Publication Date
20260512
Application Date
20150731
Priority Date
20140804

Claims (20)

  1. 1. A peptide having cytotoxic T Cell (CTL) inducibility in a HLA-A33 restricted manner consisting of the amino acid sequence of SEQ ID No. 27, 60, 28, 67 or 69.
  2. 2. A polynucleotide encoding the peptide of claim 1.
  3. 3. A composition comprising a pharmaceutically acceptable carrier and at least one ingredient selected from the following groups (a) to (e), the composition formulated for administration to a subject positive for HLA-A 33: (a) The peptide of claim 1; (b) A polynucleotide encoding the peptide of claim 1 in an expressible form; (c) An Antigen Presenting Cell (APC) that presents on its cell surface a complex of the peptide of claim 1 and an HLA-A33 antigen; (d) Exosomes presenting on their cell surfaces a complex of the peptide of claim 1 with an HLA-A33 antigen, and (E) A CTL, which targets the peptide of claim 1.
  4. 4. A composition according to claim 3, which is a composition for inducing CTLs, wherein the ingredient is at least one ingredient selected from the following groups (a) to (d): (a) The peptide of claim 1; (b) A polynucleotide encoding the peptide of claim 1 in an expressible form; (c) An Antigen Presenting Cell (APC) which presents on its cell surface a complex of the peptide of claim 1 and an HLA-A33 antigen, and (D) Exosomes presenting on their cell surfaces a complex of the peptide of claim 1 with an HLA-A33 antigen.
  5. 5. A composition according to claim 3, which is a pharmaceutical composition.
  6. 6. The composition according to claim 5 for use in one or more of the following group (i) cancer treatment, (ii) cancer prevention (prophylaxis) and (iii) prevention (prophylaxis) of postoperative cancer recurrence.
  7. 7. The composition of claim 5 for use in inducing an immune response against cancer.
  8. 8. The composition of claim 6 or 7, wherein the cancer is selected from the group consisting of bladder cancer, breast cancer, cervical cancer, cholangiocellular carcinoma, chronic Myelogenous Leukemia (CML), esophageal cancer, gastric cancer, non-small cell lung cancer, lymphoma, osteosarcoma, prostate cancer, renal cancer, small cell lung cancer, head and neck cancer, soft tissue tumor and colorectal cancer.
  9. 9. An in vitro or ex vivo method of inducing APCs having CTL inducibility comprising the step of selecting from the group consisting of: (a) Contacting in vitro or ex vivo an APC expressing HLA-A33 with a peptide according to claim 1, and (B) Introducing a polynucleotide encoding the peptide of claim 1 into an APC expressing HLA-A 33.
  10. 10. An in vitro method of inducing CTLs comprising the steps of (a) or (b) below: (a) Co-culturing CD8 positive T cells with APCs that present on their surface a complex of HLA-A33 antigen and a peptide according to claim 1, or (B) Co-culturing CD8 positive T cells with exosomes presenting on their surface a complex of HLA-A33 antigen and the peptide of claim 1.
  11. An apc which presents on its surface a complex of an HLA-A33 antigen and a peptide according to claim 1.
  12. 12. The APC according to claim 11, induced by an in vitro or ex vivo method comprising the step selected from the group consisting of: (a) Contacting in vitro or ex vivo an APC expressing HLA-A33 with a peptide according to claim 1, and (B) Introducing a polynucleotide encoding the peptide of claim 1 into an APC expressing HLA-A 33.
  13. Ctl, which targets the peptide of claim 1.
  14. 14. CTL according to claim 13, induced by an in vitro method comprising the step of (a) or (b) below: (a) Co-culturing CD8 positive T cells with APCs that present on their surface a complex of HLA-A33 antigen and a peptide according to claim 1, or (B) Co-culturing CD8 positive T cells with exosomes presenting on their surface a complex of HLA-A33 antigen and the peptide of claim 1.
  15. 15. Use of at least one member selected from the following groups (a) to (e) in the manufacture of a medicament for inducing an immune response against a CDCA1 expressing cancer in a HLA-A33 restricted manner: (a) The peptide of claim 1; (b) A polynucleotide encoding the peptide of claim 1 in an expressible form; (c) An Antigen Presenting Cell (APC) that presents on its cell surface a complex of the peptide of claim 1 and an HLA-A33 antigen; (d) Exosomes presenting on their cell surfaces a complex of the peptide of claim 1 with an HLA-A33 antigen, and (E) A CTL, which targets the peptide of claim 1.
  16. 16. Use of at least one member selected from the following groups (a) to (e) in the manufacture of a medicament for treating a CDCA1 expressing cancer in a subject positive for HLA-A 33: (a) The peptide of claim 1; (b) A polynucleotide encoding the peptide of claim 1 in an expressible form; (c) An Antigen Presenting Cell (APC) that presents on its cell surface a complex of the peptide of claim 1 and an HLA-A33 antigen; (d) Exosomes presenting on their cell surfaces a complex of the peptide of claim 1 with an HLA-A33 antigen, and (E) A CTL, which targets the peptide of claim 1.
  17. 17. A method of screening for peptides having CTL inducibility, comprising the steps of: (a) Generating a candidate sequence consisting of an amino acid sequence in which one, two or 3 or less amino acid residues are substituted for the original amino acid sequence consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs:27,60,28,67 and 69; (b) Selecting a candidate sequence from the candidate sequences generated in (a) that does not have significant homology (sequence identity) to any known human gene product other than CDCA 1; (c) Contacting an APC expressing HLA-A33 with a peptide consisting of the candidate sequence selected in (b); (d) Contacting the APC of (c) with a CD 8-positive T cell, and (E) Peptides having equal or higher CTL inducibility than peptides consisting of the original amino acid sequence were selected.
  18. 18. An emulsion comprising the peptide of claim 1, a water-soluble carrier, and an oil adjuvant.
  19. 19. A kit comprising a container comprising the composition of any one of claims 3 to 8 and a container comprising an adjuvant.
  20. 20. Use of the peptide of claim 1 or a polynucleotide encoding the peptide of claim 1 in the preparation of a composition for inducing APCs having CTL inducibility in a HLA-A33 restricted manner, wherein the inducing comprises: (a) Contacting in vitro, ex vivo or in vivo an APC expressing HLA-A33 with a peptide according to claim 1, and (B) Introducing a polynucleotide encoding the peptide of claim 1 into an APC expressing HLA-A 33.

Description

CDCA 1-derived peptides and vaccines containing the same The application is a divisional application of Chinese patent application with the application date of 2015, 7, 31, 201580052500.2 and the name of CDCA1 derived peptide and vaccine containing the same. Technical Field The invention relates to the field of bioscience, more particularly to the field of cancer treatment. In particular, the present invention relates to novel peptides effective as cancer vaccines, methods of using the peptides to treat and/or prevent tumors, and pharmaceutical compositions comprising the peptides. The present application claims the benefit of japanese patent applications filed on date 08 and 04 of 2014 (japanese patent application nos. 2014-158922, 2014-158923, and 2014-158924), the entire contents of which are incorporated herein by reference. Background Cytotoxic T Cells (CTLs) have been shown to recognize epitope peptides derived from Tumor Associated Antigens (TAAs) found on Major Histocompatibility Complex (MHC) class I molecules, and then kill tumor cells. Since the discovery of the Melanoma Antigen (MAGE) family, many other TAA(NPL1:Boon T,Int J Cancer 1993 May 8,54(2):177-80;NPL2:Boon T&van der Bruggen P,J Exp Med 1996 Mar 1,183(3):725-9). of these TAAs have been discovered by immunological methods are currently being developed clinically as immunotherapeutic targets. Among several of these TAAs, epitope peptides that can be recognized by CTLs were identified and their use in immunotherapy for various types of cancers was contemplated (NPL 3: harris CC, J NATL CANCER INST 1996 Oct 16,88 (20): 1442-55;NPL4:Butterfield LH et al, CANCER RES 1999 Jul 1,59 (13): 3134-42;NPL5:Vissers JL et al, CANCER RES 1999 Nov 1,59 (21): 5554-9;NPL6:van der Burg SH et al, J Immunol 1996 May 1,156 (9) 3308-14; NPL7: tanaka F et al, CANCER RES Oct 15,57 (20): 4465-8; NPL8: fujie T et al, int J Cancer 1999Jan 18,80 (2): 169-72;NPL9:Kikuchi M et al, int J Cancer 1999 May 5,81 (3): 439 66; NPL10: oiso M et al, int J Cancer 1999 May 5,81 (3): 387-94). Several clinical trials using these TAA-derived CTL epitope peptides have been reported to date. Unfortunately, many of these clinical trials have shown low objective response rates (NPL 11: belli F et al, J Clin Oncol 2002 Oct 15,20 (20): 4169-80;NPL12:Coulie PG et al, immunol Rev 2002 Oct,188:33-42;NPL13:Rosenberg SA et al, nat Med 2004 Sep,10 (9): 909-15). Thus, there remains a need to identify new CTL epitopes that can be used in cancer immunotherapy. CDCA1 (cell division cycle associated protein 1; also described as NUF2, NDC80 kinetochore complex component (NDC 80 kinetochore complex component): nuf2; reference sequence: geneBank accession No. NM-145697 (SEQ ID NO: 81) or GeneBank accession No. NM-031423 (SEQ ID NO: 83)) has been identified as a member of the genes co-expressed with CDC2, cyclin, topoisomerase II and other cell cycle genes (NPL 14: walker et al Curr Cancer Drug Targets 2001 May;1 (1): 73-83). CDCA1 has been found to be associated with the centromere of HeLa cells undergoing mitosis and is believed to be a functional homolog of yeast Nuf2 (NPL 15: wigge PA et al, J Cell Biol 2001 Jan 22;152 (2): 349-60). Meanwhile, CDCA1 has been identified as a gene up-regulated in non-small cell lung cancer by gene expression profiling using a whole genome cDNA microarray containing 23,040 genes (NPL 16: hayama et al, CANCER RES 2006 Nov 1;66 (21): 10339-48; PTL1: WO 2007/013180; PTL2: WO 2005/089735). CDCA1 expression was up-regulated in tumors and tumor cell lines, and was undetectable in normal organs other than testis (NPL 16; PTL 1). In addition, siRNA-mediated down-regulation of CDCA1 expression results in inhibition of cell proliferation in lung cancer cell lines expressing CDCA 1. Recently, CDCA 1-derived HLA-A2 restricted CTL epitope peptides (NPL 17: harao et al., int J cancer.2008:123 (11): 2616-25; PTL3:WO 2009/025117) and HLA-A24 restricted CTL epitope peptides (PTL 4:WO 2009/153992) have been identified. These peptides are effective in cancer patients with HLA-A2 type or HLA-A24 type, but would not be expected to have an effect on cancer patients without these HLa types. [ Reference List ] [ Patent literature ] [PTL 1]WO2007/013480 [PTL 2]WO2005/089735 [PTL 3]WO2009/025117 [PTL 4]WO2009/153992 [ Non-patent literature ] [NPL 1]Boon T,Int J Cancer 1993 May 8,54(2):177-80 [NPL 2]Boon T&van der Bruggen P,J Exp Med 1996 Mar 1,183(3):725-9 [NPL 3]Harris CC,J Natl Cancer Inst 1996 Oct 16,88(20):1442-55 [ NPL 4] Butterfield LH et al CANCER RES 1999 Jul 1,59 (13): 3134-42 [ NPL 5] Vissers JL et al CANCER RES 1999 Nov 1,59 (21): 5554-9 [ NPL 6]van der Burg SH et al, J Immunol 1996 May 1,156 (9): 3308-14 [ NPL 7] tanaka F et al CANCER RES 1997 Oct 15,57 (20): 4465-8 [ NPL 8] Fujie T et al, int J Cancer 1999 Jan 18,80 (2): 169-72 [ NPL 9] Kikuchi M et al, int J Cancer 1999 May 5,81 (3): 459-66 [ NPL 10] Oiso M et al, int J Cancer 1999 May 5,81 (3): 387-94 [ NPL 11] Bell F et al, J Cli