WO2010113495A1 - C6orf167 peptides and vaccines containing the same - Google Patents

C6orf167 peptides and vaccines containing the same Download PDF

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Publication number
WO2010113495A1
WO2010113495A1 PCT/JP2010/002352 JP2010002352W WO2010113495A1 WO 2010113495 A1 WO2010113495 A1 WO 2010113495A1 JP 2010002352 W JP2010002352 W JP 2010002352W WO 2010113495 A1 WO2010113495 A1 WO 2010113495A1
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WO
WIPO (PCT)
Prior art keywords
c6orf167
seq
peptide
cancer
peptides
Prior art date
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Ceased
Application number
PCT/JP2010/002352
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English (en)
French (fr)
Inventor
Yusuke Nakamura
Yataro Daigo
Takuya Tsunoda
Ryuji Ohsawa
Sachiko Yoshimura
Tomohisa Watanabe
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Oncotherapy Science Inc
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Oncotherapy Science Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US13/260,900 priority Critical patent/US20120128705A1/en
Priority to AU2010231381A priority patent/AU2010231381A1/en
Priority to CN201080024056.0A priority patent/CN102448980B/zh
Priority to RU2011144088/10A priority patent/RU2011144088A/ru
Priority to BRPI1013384A priority patent/BRPI1013384A2/pt
Priority to SG2011071370A priority patent/SG174998A1/en
Priority to EP10758274.4A priority patent/EP2414383A4/en
Priority to CA2757210A priority patent/CA2757210A1/en
Application filed by Oncotherapy Science Inc filed Critical Oncotherapy Science Inc
Priority to JP2011542381A priority patent/JP5728759B2/ja
Priority to MX2011010191A priority patent/MX2011010191A/es
Publication of WO2010113495A1 publication Critical patent/WO2010113495A1/en
Priority to IL215268A priority patent/IL215268A0/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/0005—Vertebrate antigens
    • A61K39/0011—Cancer antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/112—Disease subtyping, staging or classification

Definitions

  • NM_198468.2 (SEQ ID NO: 158)) is demonstrated to be specifically over-expressed in cancer cells, including bladder cancer, cervical cancer, cholangiocellular carcinoma, chronic myelogenous leukemia (CML), esophageal cancer, gastric cancer, gastric diffuse-type cancer, lung cancer, lymphoma, osteosarcoma, renal carcinoma, lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC), small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC), soft tissue tumor, and testicular tumor, but not limited thereto.
  • C6orf167 an appropriate cancer marker and candidate for the target of immunotherapy.
  • FIG. 1u-z is composed of a series of photographs, (u) - (z), depicting the results of IFN-gamma ELISPOT assays on CTLs that were induced with peptides derived from C6orf167.
  • Figure 7e-j is composed of a series of line graphs, (e) to (j), depicting the IFN-gamma production of the CTL lines stimulated with C6orf167-A02-9-484 (SEQ ID NO: 84) (e), C6orf167-A02-10-535 (SEQ ID NO: 101) (f), C6orf167-A02-10-527 (SEQ ID NO: 110) (g), C6orf167-A02-10-10 (SEQ ID NO: 111) (h), C6orf167-A02-10-577 (SEQ ID NO: 112) (i), and C6orf167-A02-10-128 (SEQ ID NO: 113) (j) detected by IFN-gamma ELISA assay.
  • C6orf167 is an antigen recognized by CTL and that the peptides are epitope peptides of C6orf167 restricted by HLA-A24 or HLA-A2.
  • CTL inducibility can be assessed by measuring IFN-gamma produced and released by CTL in the presence of APCs that carry immobilized peptides, and visualizing the inhibition zone on the media using anti-IFN-gamma monoclonal antibodies.
  • modified peptides that are substituted, deleted or added by one, two or several amino acid residues
  • those having same or higher activity as compared to original peptides can be screened for or selected.
  • the present invention also provides the method of screening for or selecting modified peptides having same or higher activity as compared to originals.
  • An illustrative method includes the steps of: a: substituting, deleting or adding at least one amino acid residue of a peptide of the present invention:, b: determining the activity of the peptide:, c: selecting the peptide having same or higher activity as compared to the original.
  • the APCs obtained by step b can be a vaccine for treating and/or preventing cancer, such as bladder cancer, cervical cancer, cholangiocellular carcinoma, chronic myelogenous leukemia (CML), esophageal cancer, gastric cancer, gastric diffuse-type cancer, lung cancer, lymphoma, osteosarcoma, renal carcinoma, lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC), small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC), soft tissue tumor and testicular tumor, but not limited thereto.
  • cancer such as bladder cancer, cervical cancer, cholangiocellular carcinoma, chronic myelogenous leukemia (CML), esophageal cancer, gastric cancer, gastric diffuse-type cancer, lung cancer, lymphoma, osteosarcoma, renal carcinoma, lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC), small-cell lung cancer (SCLC), non-small-cell
  • the APCs have a high level of CTL inducibility.
  • high level of CTL inducibility the high level is relative to the level of that by APC contacted with no peptide or peptides which can not induce the CTL.
  • Such APCs having a high level of CTL inducibility can be prepared by a method that includes the step of transferring a polynucleotide encoding the peptide of the present invention to APCs in vitro as well as the method mentioned above.
  • the introduced genes can be in the form of DNAs or RNAs.
  • CTLs Cytotoxic T lymphocytes
  • a CTL induced against any one of the peptides of the present invention strengthens the immune response targeting cancer cells in vivo and thus can be used as vaccines, in a fashion similar to the peptides per se.
  • the present invention provides isolated CTLs that are specifically induced or activated by any one of the present peptides.
  • compositions of the present invention can be used to treat and/or prevent cancers, and/or prevention of postoperative recurrence thereof in subjects or patients including human and any other mammal including, but not limited to, mouse, rat, guinea-pig, rabbit, cat, dog, sheep, goat, pig, cattle, horse, monkey, baboon, and chimpanzee, particularly a commercially important animal or a domesticated animal.
  • the present invention further provides an active ingredient selected from among: (a) a peptide of the present invention; (b) a nucleic acid encoding such a peptide as disclosed herein in an expressible form; (c) an APC or an exosome presenting a peptide of the present invention on its surface; and (d) a cytotoxic T cell of the present invention for use in treating or preventing cancer of tumor.
  • an active ingredient selected from among: (a) a peptide of the present invention; (b) a nucleic acid encoding such a peptide as disclosed herein in an expressible form; (c) an APC or an exosome presenting a peptide of the present invention on its surface; and (d) a cytotoxic T cell of the present invention for use in treating or preventing cancer of tumor.
  • the pharmaceutical compositions of the present invention can optionally include other therapeutic substances as an active ingredient, so long as the substance does not inhibit the antitumoral effect of the active ingredient, e.g., any of the present peptides.
  • formulations can include anti-inflammatory compositions, pain killers, chemotherapeutics, and the like.
  • the medicaments of the present invention can also be administered sequentially or concurrently with the one or more other pharmacologic compositions.
  • the amounts of medicament and pharmacologic composition depend, for example, on what type of pharmacologic composition(s) is/are used, the disease being treated, and the scheduling and routes of administration.
  • DNA-based delivery technologies include "naked DNA”, facilitated (bupivacaine, polymers, peptide-mediated) delivery, cationic lipid complexes, and particle-mediated (“gene gun”) or pressure-mediated delivery (see, e.g., U.S. Patent No. 5,922,687).
  • the methods of the present invention includes the step of administering the peptides, the polynucleotides, the APCs or exosomes of the present invention to a subject.
  • ADC lung adenocarcinoma
  • SCC small-cell lung cancer
  • NSCLC non-small-cell lung cancer
  • soft tissue tumor and testicular tumor.
  • C6orf167 expression was validly elevated in 13 out of bladder cancers, 2 out of 2 cervical cancers, 8 out of 11 cholangiocellular carcinomas, 20 out of 33 CMLs, 11 out of 15 esophageal cancers, 5 out of 8 gastric cancers, 2 out of 2 gastric diffuse-type cancers, 1 out of 2 lung cancers, 2 out of 2 lymphomas, 2 out of 3 osteosarcomas, 5 out of 12 renal carcinomas, 4 out of 4 SCLCs, 1 out of 1 soft tissue tumor and 1 out of 2 testicular tumors, as compared with corresponding normal tissue (Table 1).
  • C6orf167 in lung cancers, esophageal cancers and normal tissues.
  • a cDNA microarray to screen for elements that were highly transactivated in a large proportion of lung cancer (WO2007/013665) and/or esophageal cancers, the C6orf167 gene was identified as a good candidate target for diagnosing and/or treating cancers. This gene showed a higher level of expression in the majority of lung and esophageal cancers. Subsequently it was confirmed its transactivation by semiquantitative RT-PCR experiments in 7 of 10 NSCLC cases (3 of 5 ADCs and 4 of 5 SCCs) and in all of 5 SCLC cases (Fig.
  • CTL activity was tested on the 14th day, and CTL clones were expanded using the same method as described above (Uchida N et al., Clin Cancer Res 2004 Dec 15, 10(24): 8577-86; Suda T et al., Cancer Sci 2006 May, 97(5): 411-9; Watanabe T et al., Cancer Sci 2005 Aug, 96(8): 498-506).
  • the cDNA encoding an open reading frame of target genes or HLA-A*0201 was amplified by PCR.
  • the PCR-amplified product was cloned into pCAGGS vector and pIRES vector (Clontech Laboratories, Inc., Cat. No. 631605).
  • the plasmids were transfected into COS7, which is the target genes and HLA-A*0201-null cell line, using lipofectamine 2000 (Invitrogen) according to the manufacturer's recommended procedures. After 2 days from transfection, the transfected cells were harvested with versene (Invitrogen) and used as the target cells (5 x 10 4 cells/ well) for CTL activity assay.
  • Specific CTL activity against target cells exogenously expressing C6orf167 and HLA-A*0201 The established CTL lines and clones raised against each peptide were examined for the ability to recognize target cells that endogenously express C6orf167 and HLA-A*0201 molecule.
  • Specific CTL activity against COS7 cells which transfected with both the full length of C6orf167 and HLA-A*0201 gene was tested by using the CTL lines and clones raised by corresponding peptide as the effector cells.
  • COS7 cells transfected with either full length of C6orf167 or HLA-A* 0201 were prepared as the controls.
  • the present invention provides new TAAs, particularly those derived from C6orf167 which may induce potent and specific anti-tumor immune responses and have applicability to a wide variety of cancer types.
  • TAAs can find utility as peptide vaccines against diseases associated with C6orf167, e.g., cancer, examples of which include, but are not limited to, bladder cancer, cervical cancer, cholangiocellular carcinoma, chronic myelogenous leukemia (CML), esophageal cancer, gastric cancer, gastric diffuse-type cancer, lung cancer, lymphoma, osteosarcoma, renal carcinoma, lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC), small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC), soft tissue tumor and testicular tumor.
  • cancer examples of which include, but are not limited to, bladder cancer, cervical cancer, cholangiocellular carcinoma, chronic myelogenous leukemia (CML), esophageal cancer

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Oncology (AREA)
  • Microbiology (AREA)
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  • Analytical Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
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  • Hospice & Palliative Care (AREA)
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  • Wood Science & Technology (AREA)
  • Urology & Nephrology (AREA)
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PCT/JP2010/002352 2009-04-01 2010-03-31 C6orf167 peptides and vaccines containing the same Ceased WO2010113495A1 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
EP10758274.4A EP2414383A4 (en) 2009-04-01 2010-03-31 C6ORF167 PEPTIDES AND VACCINES CONTAINING THEM
CN201080024056.0A CN102448980B (zh) 2009-04-01 2010-03-31 C6orf167肽及包含它的疫苗
RU2011144088/10A RU2011144088A (ru) 2009-04-01 2010-03-31 ПЕПТИДЫ С6orf167 И СОДЕРЖАЩИЕ ИХ ВАКЦИНЫ
BRPI1013384A BRPI1013384A2 (pt) 2009-04-01 2010-03-31 peptídeos c6orf167 e vacinas incluindo os mesmos
SG2011071370A SG174998A1 (en) 2009-04-01 2010-03-31 C6orf167 peptides and vaccines containing the same
US13/260,900 US20120128705A1 (en) 2009-04-01 2010-03-31 C6orf167 peptides and vaccines containing the same
MX2011010191A MX2011010191A (es) 2009-04-01 2010-03-31 Peptidos c6orf167 y vacunas que continen los mismos.
CA2757210A CA2757210A1 (en) 2009-04-01 2010-03-31 C6orf167 peptides and vaccines containing the same
JP2011542381A JP5728759B2 (ja) 2009-04-01 2010-03-31 Ｃ６ｏｒｆ１６７ペプチドおよびそれを含むワクチン
AU2010231381A AU2010231381A1 (en) 2009-04-01 2010-03-31 C6orf167 peptides and vaccines containing the same
IL215268A IL215268A0 (en) 2009-04-01 2011-09-21 C6orf167 peptides and vaccines containing the same

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US21170009P 2009-04-01 2009-04-01
US61/211,700 2009-04-01

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WO2010113495A1 true WO2010113495A1 (en) 2010-10-07

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US (1) US20120128705A1 (enExample)
EP (1) EP2414383A4 (enExample)
JP (1) JP5728759B2 (enExample)
KR (1) KR20120034605A (enExample)
CN (2) CN102448980B (enExample)
AU (1) AU2010231381A1 (enExample)
BR (1) BRPI1013384A2 (enExample)
CA (1) CA2757210A1 (enExample)
IL (1) IL215268A0 (enExample)
MX (1) MX2011010191A (enExample)
RU (1) RU2011144088A (enExample)
SG (2) SG2014011423A (enExample)
TW (1) TW201100090A (enExample)
WO (1) WO2010113495A1 (enExample)

Cited By (3)

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Publication number Priority date Publication date Assignee Title
WO2012023259A1 (en) * 2010-08-19 2012-02-23 Oncotherapy Science, Inc. C6orf167 as a target gene for cancer therapy and diagnosis
US8771963B2 (en) 2005-07-27 2014-07-08 Oncotherapy Science, Inc. Method of diagnosing esophageal cancer
US9403890B2 (en) 2010-03-11 2016-08-02 Oncotherapy Science, Inc. HJURP peptides and vaccines including the same

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WO2007013665A2 (en) * 2005-07-27 2007-02-01 Oncotherapy Science, Inc. Method of diagnosing small cell lung cancer
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8771963B2 (en) 2005-07-27 2014-07-08 Oncotherapy Science, Inc. Method of diagnosing esophageal cancer
US9403890B2 (en) 2010-03-11 2016-08-02 Oncotherapy Science, Inc. HJURP peptides and vaccines including the same
AU2011225577B2 (en) * 2010-03-11 2017-01-19 Oncotherapy Science, Inc. HJURP peptides and vaccines including the same
US9896492B2 (en) 2010-03-11 2018-02-20 Oncotherapy Science, Inc. HJURP peptides and vaccines including the same
WO2012023259A1 (en) * 2010-08-19 2012-02-23 Oncotherapy Science, Inc. C6orf167 as a target gene for cancer therapy and diagnosis

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SG174998A1 (en) 2011-11-28
EP2414383A4 (en) 2013-07-31
TW201100090A (en) 2011-01-01
EP2414383A1 (en) 2012-02-08
CN104774260A (zh) 2015-07-15
BRPI1013384A2 (pt) 2016-03-29
CA2757210A1 (en) 2010-10-07
US20120128705A1 (en) 2012-05-24
CN102448980A (zh) 2012-05-09
MX2011010191A (es) 2011-11-29
RU2011144088A (ru) 2013-05-10
JP5728759B2 (ja) 2015-06-03
KR20120034605A (ko) 2012-04-12
AU2010231381A1 (en) 2011-11-03
CN102448980B (zh) 2015-04-15
JP2012522488A (ja) 2012-09-27
IL215268A0 (en) 2011-11-30
SG2014011423A (en) 2014-05-29

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