WO2006077941A1 - Vaccin contre le cancer - Google Patents

Vaccin contre le cancer Download PDF

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Publication number
WO2006077941A1
WO2006077941A1 PCT/JP2006/300764 JP2006300764W WO2006077941A1 WO 2006077941 A1 WO2006077941 A1 WO 2006077941A1 JP 2006300764 W JP2006300764 W JP 2006300764W WO 2006077941 A1 WO2006077941 A1 WO 2006077941A1
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WIPO (PCT)
Prior art keywords
cells
cancer
cell
sox6
antigen
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PCT/JP2006/300764
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English (en)
Japanese (ja)
Inventor
Masahiro Toda
Ryo Ueda
Kozo Tsukada
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Keio University
Institute Of Gene And Brain Science
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Priority to JP2006553954A priority Critical patent/JP4840866B2/ja
Publication of WO2006077941A1 publication Critical patent/WO2006077941A1/fr

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    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • C07K14/4705—Regulators; Modulating activity stimulating, promoting or activating activity
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/461—Cellular immunotherapy characterised by the cell type used
    • A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/461—Cellular immunotherapy characterised by the cell type used
    • A61K39/4615—Dendritic cells
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
    • A61K39/4622—Antigen presenting cells
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • A61K39/464452—Transcription factors, e.g. SOX or c-MYC
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a cancer vaccine.
  • antigen-presenting cells dendritic cells or DCs
  • MHC human leukocyte antigen or HLA in humans
  • Cytotoxic T lymphocytes cytotoxic T lymphocytes or CTLs
  • HLA class I human leukocyte antigen or HLA in humans
  • cancer vaccines have been developed as a method for treating tumors.
  • dendritic cells that present antigenic peptides derived from tumor-specific proteins on the cell surface are generated in vitro, proliferated, administered to tumor patients, and cytotoxic T cells educated by the dendritic cells.
  • Tumor immunity is induced in the body of tumor patients by administering cells.
  • a tumor-specific protein is administered to a tumor patient to induce the whole process of the tumor immune mechanism in the patient's body (Science (1991) 254: 1643-1647; Exp. Med. (1 996) 183: 1185-1192; J. Immunol. (1999) 163: 4994- 5004; Proc. Natl. Acad. Sci. US A (1995) 92: 432 -436; Science (1995) 269: 1281— 1284; J. Exp. Med. (1997) 186: 7 85—793).
  • tumor reduction has been observed in 42% of patients by subcutaneous administration of melanoma antigen gplOO peptide to melanoma patients and intravenous administration of interleukin 2 (Nature Medicine (1998) 4: 321) Disclosure of the invention
  • the present invention provides a peptide capable of efficiently inducing tumor immunity, a composition containing the peptide, an antigen-presenting cell presenting the peptide, a ⁇ cell stimulated by the antigen-presenting cell, and these
  • the purpose of the present invention was to provide a cancer vaccine using these peptides and cells, and a method for treating tumor patients using them.
  • the present inventors have already found that the transcription factor SOX6 is expressed in Darioma (Ueda et al "Oncogene 23, 1420-1427, 2004). (See Example 2) Based on this finding, whether various partial peptides of SOX6 are recognized by cytotoxic T cells in a HLA class I-restricted manner As a result, it was possible to identify several partial peptides that were efficiently recognized by cytotoxic T cells when added to dendritic cells, and the present invention was completed.
  • the peptide according to the present invention has any one of SEQ ID NOs:!
  • Antigen presenting cells presenting these peptides and T cells that are recognized by the antigen presenting cells and recognize cells expressing SOX 6 also belong to the technical scope of the present invention.
  • These T cells are preferably cytotoxic T cells.
  • Cells expressing SOX6 are Darioma, liver cancer cells, lung cancer cells, knee cancer cells, esophageal cancer cells, melanoma cells, prostate cancer cells, breast cancer cells. Cell, renal cancer cell, or leukemia cell.
  • the cancer vaccine according to the present invention contains at least one of one or more peptides selected from SEQ ID NOs:! To 3, the antigen-presenting cells, and the T cells.
  • This cancer vaccine is a cancer vaccine against cancer cells that express SOX6, especially cancers against cell dario, liver cancer, lung cancer, vaginal cancer, esophageal cancer, melanoma, prostate cancer, breast cancer, kidney cancer, or leukemia It is preferable to be a vaccine.
  • the tumor treatment method according to the present invention is characterized by using this cancer vaccine against humans and non-human vertebrates. [0011] Cross-reference with related literature
  • FIG. 1 shows cytotoxic T cells induced by co-culture with dendritic cells to which a peptide derived from SO X6 predicted to bind to HLA-A24 in the examples of the present invention was added.
  • FIG. 3 is a graph showing the results of measuring IFN- ⁇ released when effector cells are co-cultured with a rod-shaped cell presenting these HLA-A24-binding SOX6-derived peptides as a target.
  • FIG. 2A shows the results of SOX6 expression analysis by quantitative RT-PCT in the examples of the present invention.
  • FIG. 2B is a diagram showing the results of SOX6 expression analysis by Western * blotting in the examples of the present invention.
  • FIG. 3 In the examples of the present invention, cytotoxic T cells (effector cells) induced by co-culture with dendritic cells to which a peptide derived from SO X6, which is expected to bind to HLA-A24, was added. ) Is a graph showing the results of measurement of IFN- ⁇ released when co-cultured with Dario cells that express HLA_A24 and SOX6 (K NS-81) as a target.
  • HLA-A2402 was isolated from healthy human peripheral blood and induced by co-culture with dendritic cells supplemented with SOX6-derived peptides SOX6-504 and SOX6_628. Specificity of target cells calculated when CIR-A2402, CIR-A2402-SOX6, Marcus, SF126, KNS-42, HepG2, and PC9 are cocultured with cytotoxic T cells (CTL: effector cells) It is the graph which showed the typical dissolution rate.
  • CTL effector cells
  • HLA-A2402 is induced by co-culture with rod cells isolated from peripheral blood of Darioma patients and supplemented with SOX6-derived peptides SOX6-504 and SOX6-628.
  • CIR-A2402, CIR—A2402—SOX6, Marcus, SF126, and KNS—42 are targeted against cytotoxic T cells (CTL: effector cells). This is a graph showing the specific lysis rate of target cells, calculated when co-cultured as a target cell.
  • FIG. 6 HLA-A2402 isolated from healthy human peripheral blood and added with SOX6-derived peptide SOX6-504 (A) or SOX6-628 (B)
  • CTL cytotoxic T cells
  • A Marcus
  • CIR—A2402 S ⁇ X6—504
  • CIR—A2402 CIR—A2402
  • CIR—A2402 or B FIG. 3 is a graph showing the specific lysis rate of target cells calculated when co-cultured with Marcus, CIR-A2402 (SOX6-628), CIR-A2402 (CMV), and CIR-A2402 as target cells.
  • the SOX6 gene is encoded using the HLA Peptide Binding predictions Program of Biolnformatics & Molecular Analysis Section (BIMAS) From the amino acid sequence to be identified, a peptide sequence of 9 to 10 amino acid residues having high binding to HLA class I was identified.
  • Japanese HLA class I types are mostly 1 and 8 and 2 and 11 and 8 and 24, covering about 80% of all Japanese people.
  • the gene types of HLA-A which are common in Japanese, include A0201 and A0206 for HLA-A2, and A2402 for HLA-A24.
  • the cell genotypes are A0201 and A2402. In this case, it means having at least one allele described.
  • Table 1 shows examples of high-scoring peptide sequences obtained by this screening.
  • the tumor to be treated can be any tumor that expresses SOX6.
  • SOX6 is at a high level.
  • Darioma, liver cancer, lung cancer, knee cancer, esophageal cancer, melanoma, prostate cancer, breast cancer, kidney cancer, or leukemia that are expressed are also treated.
  • the main treatment target is a human patient having such a tumor, but a non-human vertebrate having a tumor may be used.
  • a cancer vaccine to be administered to a patient having a tumor to be treated may contain a peptide having SEQ ID NOS: 1 to 3 that can be a tumor-specific cancer antigen.
  • the peptide of SEQ ID NO:!-3 is administered.
  • the peptide to be administered may be one kind or plural kinds.
  • intradermal administration, subcutaneous administration, intravenous administration, intraperitoneal administration, and the like can be considered, and there is no particular limitation.
  • the peptide may be administered together with an adjuvant that enhances immunity induction ability.
  • the peptide to be administered may be modified so as to be degraded in vivo.
  • the cancer vaccine may contain antigen-presenting cells presenting peptides having SEQ ID NOs:! To 3.
  • the peptide displayed on the cell surface may be modified with sugar or phosphoric acid, which may be the peptide itself having SEQ ID NOs:! To 3.
  • macrophages and B cells can be considered as antigen-presenting cells.
  • Dendritic cells are preferred because of their high antigen-presenting ability.
  • an example of a method for isolating dendritic cells will be described.
  • mononuclear cells are isolated from the peripheral blood of vertebrate individuals.
  • the mononuclear cells are preferably isolated from the individual to be treated, but may be isolated from other individuals.
  • the mononuclear cells are preferably CD14 positive.
  • the isolated mononuclear cells can be induced to differentiate into immature dendritic cells by culturing with GM-CSF and IL-4 seven days later.
  • the dendritic cells thus induced to differentiate highly express MHC molecules, which are antigen-presenting molecules.
  • This immature dendritic cell is examined for HLA class I type and, if it is A24, SEQ ID NO:! ⁇ 3 Add the peptide.
  • the antigen-presenting rod cells are administered to an individual having a tumor.
  • intradermal administration subcutaneous administration, intravenous administration, intralymphatic administration, and the like can be considered, and there is no particular limitation.
  • Physical dendritic cell antigen presentation is Given that it is done in the regional lymph nodes, direct administration into the lymph nodes is preferred.
  • the cancer vaccine may contain T cells established by stimulation of antigen-presenting cells presenting peptides derived from SEQ ID NOs:! To 3. T cells are co-cultured with the antigen-presenting cells presenting peptides derived from SEQ ID NOs:! To 3 and stimulated with the antigen-presenting cells. T cells established in this way may be administered to individuals with tumors.
  • the T cell here is preferably a cytotoxic T cell, but may be a helper T cell or the like.
  • intradermal administration, subcutaneous administration, intravenous administration, intratumoral administration, etc. are conceivable, and there is no particular limitation. In the case of cytotoxic T cells, cells expressing antigen can be directly attacked. Therefore, intratumoral administration is preferred.
  • Mononuclear cells were isolated from peripheral blood of healthy individuals with HLA class 1 type A24 (genotype A2402) as follows. First, 50 ml of peripheral blood was collected with a syringe washed with 5 ml of heparin. Equal volume of Lymphoprep (Fresenius kabi Norge AS, Axis-Shield PoC AS, Oslo, Norway), mix by inverting, centrifuge (20 ° C, 2000 rpm, 35 minutes, without brake), and aspirate the middle layer did. PBS was added to this to re-turbidize, and centrifugation (20 ° C, 2000 rpm, 10 minutes) was repeated 3 times to wash the resulting mononuclear cells.
  • Lymphoprep Frsenius kabi Norge AS, Axis-Shield PoC AS, Oslo, Norway
  • the mononuclear cells were seeded in a culture dish for primary cell culture (FALCON MULTIWELL PRIMARIA 24 well) at a density of 5xl0 6 cells / well and cultured at 37 ° C in the presence of 5% CO for 4 hours. culture
  • the solution used was a mixture of AIM-V (GIBCO) and RPMI-1640 1: 1 (basic culture solution).
  • Cells that adhere to the bottom of the culture dish are collected, seeded in a new 24-well culture dish at a density of 4 ⁇ 10 5 cells / well, and basic culture with GM-CSF (10 ng / ml) and IL_4 (lng / ml) added 37 Using liquid The cells were cultured for 7 days in the presence of 5% CO at ° C to differentiate the rod cells.
  • Dendritic cells differentiated on the 7th day of culture were used as antigen presenting cells (APCs). After irradiate (60 Gy) the obtained dendritic cells, add ' ⁇ ⁇ of the synthetically purified peptide (SEQ ID NO:! ⁇ 3 and 5 SOX6-derived peptides), and 37 ° C, 5% CO
  • CMV cytomegalovirus
  • responder cells co-cultured with stimulating cells were collected from day 7 of culture, and co-cultured with newly prepared stimulated cells in the same manner.
  • the culture broth used in the above culture broth used on the 7th day of culture did not contain IL-12.
  • a 96-well culture dish was used instead of a 24-well culture dish that started culturing mononuclear cells, and seeded and cultured at 4 ⁇ 10 4 cells / well.
  • the dendritic cells differentiated using mononuclear cells cultured at 96 wels were labeled with S ⁇ , 0.1 ⁇ ⁇ , and SXX6-derived peptides with concentrations of ⁇ M, 0.1 ⁇ M, 1 ⁇ , and ⁇ .
  • the cells were cultured for 2 hours to bind to the cells, washed twice with PBS, and used as target cells. Responding cells that continued co-culture were collected, and cells adjusted to 4 ⁇ 4xl0 effector cells were added to the newly prepared target cell wells and co-cultured.
  • the culture supernatant was also collected for the above-mentioned co-culture power, and IFN- ⁇ ELISA was performed as follows.
  • the absorbance at 450 nm was measured with a reader, and the concentration of IFN- ⁇ was calculated from a standard curve prepared in advance with a known concentration of IFN- ⁇ . The results are shown in FIG.
  • Cells as material for isolating RNA were obtained as follows. First of all, Dario Imaho Tsukibutsu SF ⁇ 2b and Marcus purchased from the Health Science Research Resources Bank (Osaka, Japan). U-87-MG and T98G (glioma), GI-1 (gliosarcoma), 888mel, 928mel and 586mel (melanoma) Molt4 (leukemia and lymphoma), PC9, LU99, LK2, RERF— LC—MA (lung cancer), RCCb and RCC8 (renal cell cancer), TE8 (esophageal cancer), PK1 and PK59 (pancreas cancer), and MDA231 (breast cancer) were purchased from American Type Culture Collection (Manassas, VA).
  • the Dario-Ima organization was obtained from tumor specimens from surgical patients who had consented to the explanation from the Keio University Ethics Committee approval (No. 12-21-2). This Total RNA was isolated from these cell lines or tissues using RNeasy (Qiagen). In addition, total human normal tissue RNA was purchased from CLONTECH Laboratories, Inc. A reverse transcription reaction was performed using these total RNAs (AMV Reverse transcriptase XL (Takara Bio In, Ohtsujapan)) and oligo dT primers to synthesize cDNA.
  • the primer for j3 _actin as an internal control is
  • SOX6 has been reported to be expressed in human fetal brain, adult testis, Dariooma cell line, Dariooma tissue, melanoma, small cell lung cancer, non-small cell lung cancer, squamous lung cancer, esophagus Expression was also detected in cell lines derived from cancer, sputum cancer, prostate cancer, breast cancer, kidney cancer, chronic myeloid leukemia, and T cell leukemia. ( Figure 2A).
  • SOX6 protein in normal tissues was not detected except in testis (Fig. 2B). Furthermore, SOX6 can be detected in lung cancer cell lines (PC9), hepatocellular carcinoma lines (HepG2), and knee cancer lines (Panc-1), which are not limited to the glioma cell lines (Marcus, U87, KNS_42, SF1 26). In the meantime, expression was also detected at the protein level.
  • PC9 lung cancer cell lines
  • HepG2 hepatocellular carcinoma lines
  • Panc-1 knee cancer lines
  • effector cells were prepared in the same manner as in Example 1.
  • the HLA class 1 type of healthy individuals who obtain mononuclear cells is A24 (genotype is A2402)
  • the peptide of SEQ ID NO: 1-3 is used as the added peptide
  • the CMV-derived peptide as the control peptide SEQ ID NO: 4: QYDPVAALFF was used.
  • HLA_A24 and SOX6, but not HLA-A2 are cultured for 60 minutes, washed 5 times with PBS, and then a 96-well culture dish (COSTER 3595-96 well) And adjusted to 5xl0 3 / well and seeded as target cells.
  • Cytotoxic T cells (effector cells) induced with partial peptides derived from SOX6 (SOX6-504 and SOX6_628) respond to target cells, Dario cells (KNS-81).
  • the amount of IFN- ⁇ released increased in a cell number ratio-dependent manner compared to the control (Fig. 3). This is because T cells established by stimulation with antigen-presenting cells presenting SOX6-504 or SOX6-628 are Dario cells (KNS— expressing SOX6 and HLA-24). 81) can be specifically recognized. Since the established T cells do not react with U87 (cells that express both HLA-A201 and SOX6 but not HLA-A24), these SOX6-specific T cells are antigenically restricted to HLA-A24. Was shown to recognize.
  • effector cells were prepared in the same manner as in Example 1.
  • the type of HLA class 1 of the person who obtains mononuclear cells was A24 (A2402), and the peptides of SEQ ID NOS: 1 and 2 were used as added peptides.
  • the peripheral blood for obtaining mononuclear cells was also Darioma patient peripheral blood (results are shown in FIG. 5), which is not limited to normal human peripheral blood (results are shown in FIG. 4).
  • HIR-A B-deficient human B cell line CIR-A2402 with HLA-A2402 cDN A introduced into CIR
  • CIR-A02 with HLA-A0201 cDNA and S ⁇ X6 gene introduced into CIR 01—S ⁇ X6, HLA—Dario cells that express both A24 and SOX6 (Marcus, SF 126, KNS—42), other cancer cells that express both HLA—A24 and SOX6 (hepatocytes) Cancer-derived HepG2 and lung cancer-derived PC9) were prepared.
  • the expression of SOX6 in CIR-A2402-SOX6 cells and CIR-A0201-SOX6 cells was confirmed by the above Western blotting (FIG. 2B).
  • CIR— A24 SOX6, Gliooma cell-derived Marcus, Gliooma cell-derived SF126, Dariooma cell-derived KNS—42, Liver cancer-derived HepG2, Lung cancer-derived PC9 are cells expressing HLA-A24 and SOX6 is there.
  • Fig. 4 when CTL was induced from peripheral blood lymphocytes derived from healthy subjects
  • Fig. 5 when CTL was induced from peripheral blood lymphocytes derived from healthy subjects
  • CTL (SOX6-504) and CTL (SOX6 _628), which are cytotoxic T cells (effector cells) stimulated by co-culture with dendritic cells supplemented with 30 6 _ 628, are HLA— Cells expressing A24 and SOX6 were lysed in an E / T ratio dependent manner.
  • CIR-A2402 (SOX6-504) or a sequence in which peptide SOX6-504 having SEQ ID NO: 1 is bound to CIR_A2402, expressing HLA-A24 and SOX6 CIR_A2402 conjugated with peptide SOX6-628 having number 2 (S ⁇ X6_628)
  • CIR-A2402 (CMV) in which an irrelevant peptide derived from CMV (SEQ ID NO: 4) was bound to CIR-A2402
  • CTL (SOX6-504) and CTL (SOX6-628) bind to Marcus and SOX6-derived peptides SOX6-504 or SOX6-628 that express both HLA-A24 and SOX6.
  • the dissolution rate for CIR-A2402 was higher than the dissolution rate for CIR-A2402 to which a peptide, an irrelevant peptide was bound, and untreated CIR-A2402.
  • This force, et al., CTL (SOX6-504) and CTL (SOX6-628) are respectively SOX6-504 and It was shown that cell damage was specifically caused to cells that presented SOX6-628.
  • antigen-presenting cells presenting these antigenic peptides can be prepared using peptides having the sequences 1 to 3 derived from SOX6, and further, each of the antigen-presenting cells can be stimulated by the stimulation. Specific T cells that recognize SOX6 expressing cells as well as peptides are induced.
  • a peptide capable of efficiently inducing tumor immunity a composition containing the peptide, an antigen-presenting cell presenting the peptide, a T cell stimulated by the antigen-presenting cell, and these peptides It is now possible to provide cancer vaccines using cells and cells, and methods for treating tumor patients using them.

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Abstract

L’invention concerne l’induction efficace d’une immunité tumorale, en administrant aux patients atteints d’une tumeur un peptide partiel de SOX6 en tant que vaccin, ayant l’une quelconque des SEQ ID NOS: 1 à 3, ou des cellules présentant des antigènes, telles que des cellules dendritiques présentant un antigène dérivé du peptide, ou des lymphocytes T cytotoxiques ayant été stimulés par les cellules présentant les antigènes.
PCT/JP2006/300764 2005-01-19 2006-01-19 Vaccin contre le cancer WO2006077941A1 (fr)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008106052A (ja) * 2006-09-26 2008-05-08 Toray Ind Inc 免疫誘導剤及びその用途
WO2008081581A1 (fr) * 2007-01-03 2008-07-10 Oncotherapy Science, Inc. Vaccin à peptide foxp3
WO2009072555A1 (fr) * 2007-12-04 2009-06-11 Keio University Vaccin contre le cancer
WO2010032696A1 (fr) * 2008-09-18 2010-03-25 学校法人慶應義塾 Procédé de diagnostic et procédé thérapeutique pour le cancer

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004112829A2 (fr) * 2003-05-23 2004-12-29 Genentech, Inc. Compositions et procedes pour le diagnostic et le traitement de tumeurs d'origine gliale

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003046182A1 (fr) * 2001-11-30 2003-06-05 Institute Of Gene And Brain Science Antigene de gliome humain d'origine testiculaire

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004112829A2 (fr) * 2003-05-23 2004-12-29 Genentech, Inc. Compositions et procedes pour le diagnostic et le traitement de tumeurs d'origine gliale

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008106052A (ja) * 2006-09-26 2008-05-08 Toray Ind Inc 免疫誘導剤及びその用途
WO2008081581A1 (fr) * 2007-01-03 2008-07-10 Oncotherapy Science, Inc. Vaccin à peptide foxp3
JP2010514669A (ja) * 2007-01-03 2010-05-06 オンコセラピー・サイエンス株式会社 Ｆｏｘｐ３ペプチドワクチン
US8563516B2 (en) 2007-01-03 2013-10-22 Oncotherapy Science, Inc. Foxp3 peptide vaccine
WO2009072555A1 (fr) * 2007-12-04 2009-06-11 Keio University Vaccin contre le cancer
WO2010032696A1 (fr) * 2008-09-18 2010-03-25 学校法人慶應義塾 Procédé de diagnostic et procédé thérapeutique pour le cancer
US8323659B2 (en) 2008-09-18 2012-12-04 Keio University Method for diagnosing and/or treating tumor
CN102215870B (zh) * 2008-09-18 2013-11-20 学校法人庆应义塾 癌症的诊断方法和治疗方法

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JPWO2006077941A1 (ja) 2008-06-19

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