WO2018138257A1 - Nouveaux peptides et combinaison de peptides à utiliser en immunothérapie contre le cancer de l'ovaire et d'autres cancers - Google Patents

Nouveaux peptides et combinaison de peptides à utiliser en immunothérapie contre le cancer de l'ovaire et d'autres cancers Download PDF

Info

Publication number
WO2018138257A1
WO2018138257A1 PCT/EP2018/051952 EP2018051952W WO2018138257A1 WO 2018138257 A1 WO2018138257 A1 WO 2018138257A1 EP 2018051952 W EP2018051952 W EP 2018051952W WO 2018138257 A1 WO2018138257 A1 WO 2018138257A1
Authority
WO
WIPO (PCT)
Prior art keywords
peptide
cancer
cell
peptides
seq
Prior art date
Application number
PCT/EP2018/051952
Other languages
English (en)
Inventor
Heiko Schuster
Janet PEPER
Kevin RÖHLE
Philipp Wagner
Hans-Georg Rammensee
Original Assignee
Immatics Biotechnologies Gmbh
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 SI201830920T priority Critical patent/SI3573647T1/sl
Priority to RS20230396A priority patent/RS64217B1/sr
Priority to CN201880008006.XA priority patent/CN110198734A/zh
Priority to HRP20230512TT priority patent/HRP20230512T8/hr
Application filed by Immatics Biotechnologies Gmbh filed Critical Immatics Biotechnologies Gmbh
Priority to EA201991444A priority patent/EA201991444A1/ru
Priority to MA47367A priority patent/MA47367B1/fr
Priority to LTEPPCT/EP2018/051952T priority patent/LT3573647T/lt
Priority to JP2019539937A priority patent/JP7337695B2/ja
Priority to KR1020197022277A priority patent/KR20190112271A/ko
Priority to CR20190388A priority patent/CR20190388A/es
Priority to AU2018212584A priority patent/AU2018212584B2/en
Priority to NZ754139A priority patent/NZ754139A/en
Priority to CR20210128A priority patent/CR20210128A/es
Priority to ES18702642T priority patent/ES2946584T3/es
Priority to EP18702642.2A priority patent/EP3573647B1/fr
Priority to SG11201906198PA priority patent/SG11201906198PA/en
Priority to CR20210129A priority patent/CR20210129A/es
Priority to MX2019008843A priority patent/MX2019008843A/es
Priority to CR20210130A priority patent/CR20210130A/es
Priority to EP22151693.3A priority patent/EP4035675A3/fr
Priority to IL299051A priority patent/IL299051A/en
Priority to BR112019015237A priority patent/BR112019015237A2/pt
Priority to CA3048108A priority patent/CA3048108A1/fr
Publication of WO2018138257A1 publication Critical patent/WO2018138257A1/fr
Priority to PH12019501377A priority patent/PH12019501377A1/en
Priority to IL268278A priority patent/IL268278B2/en
Priority to CONC2019/0008008A priority patent/CO2019008008A2/es
Priority to AU2021201346A priority patent/AU2021201346A1/en
Priority to AU2021201350A priority patent/AU2021201350B9/en
Priority to AU2021201349A priority patent/AU2021201349A1/en
Priority to AU2021201348A priority patent/AU2021201348A1/en
Priority to AU2021201347A priority patent/AU2021201347A1/en
Priority to JP2023135232A priority patent/JP2023179415A/ja

Links

Classifications

    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70539—MHC-molecules, e.g. HLA-molecules
    • 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
    • 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
    • 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
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—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
    • C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2833—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against MHC-molecules, e.g. HLA-molecules
    • 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
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B30/00—ICT specially adapted for sequence analysis involving nucleotides or amino acids
    • 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
    • A61K2039/80—Vaccine for a specifically defined cancer
    • A61K2039/892—Reproductive system [uterus, ovaries, cervix, testes]
    • 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
    • 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
    • A61K39/001102—Receptors, cell surface antigens or cell surface determinants
    • 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
    • A61K39/001136—Cytokines
    • A61K39/001138—Tumor necrosis factors [TNF] or CD70
    • 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
    • A61K39/001148—Regulators of development
    • 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
    • A61K39/001148—Regulators of development
    • A61K39/001149—Cell cycle regulated proteins, e.g. cyclin, CDC, CDK or INK-CCR
    • 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
    • A61K39/001152—Transcription factors, e.g. SOX or c-MYC
    • 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
    • A61K39/001154—Enzymes
    • 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
    • A61K39/001154—Enzymes
    • A61K39/001162—Kinases, e.g. Raf or Src
    • 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
    • A61K39/001154—Enzymes
    • A61K39/001163—Phosphatases
    • 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
    • A61K39/001166—Adhesion molecules, e.g. NRCAM, EpCAM or cadherins
    • 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
    • A61K39/001169—Tumor associated carbohydrates
    • A61K39/00117—Mucins, e.g. MUC-1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • 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
    • C12Q2600/156—Polymorphic or mutational markers

Definitions

  • Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers are novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
  • the present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods.
  • the present invention relates to the immunotherapy of cancer.
  • the present invention furthermore relates to tumor- associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients.
  • Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.
  • MHC major histocompatibility complex
  • the present invention relates to several novel peptide sequences and their variants derived from HLA class I and HLA class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses, or as targets for the development of pharmaceutically / immunologically active compounds and cells.
  • ovarian cancer is the seventh most common cancer in women, representing 4% of all cancers in women.
  • the fatality rate of ovarian cancer tends to be rather high relative to other cancers of the female reproductive organs, and case fatality is higher in lower-resource settings. Therefore, ovarian cancer is the eighth most frequent cause of cancer death among women, with 152 000 deaths.
  • In 2012 almost 55% of all new cases occurred in countries with high or very high levels of human development; 37% of the new cases and 39% of the deaths occurred in Europe and North America. Incidence rates are highest in northern and eastern Europe, North America, and Oceania, and tend to be relatively low in Africa and much of Asia. Incidence rates have been declining in certain countries with very high levels of human development, notably in Europe and North America.
  • ovarian carcinomas are also the most lethal gynecological malignancies. Based on histopathology and molecular genetics, ovarian carcinomas are divided into five main types: high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3%), and low-grade serous carcinomas ( ⁇ 5%), which together account for more than 95% of cases. Much less common are malignant germ cell tumors (dysgerminomas, yolk sac tumors, and immature teratomas) (3% of ovarian cancers) and potentially malignant sex cord stromal tumors (1-2%), the most common of which are granulosa cell tumors.
  • Ovarian carcinomas most commonly affect nulliparous women and occur least frequently in women with suppressed ovulation, typically by pregnancy or oral contraceptives. These tumors are generally considered to originate from the cells covering the ovarian surface or the pelvic peritoneum. Malignant transformation of this mesothelium has been explained by the "incessant ovulation" theory (La, 2001 ).
  • Surgical resection is the primary therapy in early as well as advanced stage ovarian carcinoma. The ultimate goal is the complete removal of the tumor mass in healthy surrounding tissue. Surgical removal is followed by systemic chemotherapy with platinum analogs, except for very low grade ovarian cancers (stage IA, grade 1 ), where post-operative chemotherapy is not indicated.
  • stage IA very low grade ovarian cancers
  • the first line chemotherapy comprises a combination of carboplatin with paclitaxel, which can be supplemented with bevacizumab.
  • the standard treatment for platinum-resistant ovarian cancers consists of a monotherapy with one of the following chemotherapeutics: pegylated liposomal doxorubicin, topotecane, gemcitabine or paclitaxel (S3-Leitline maligne Ovarialtumore, 2013).
  • Immunotherapy appears to be a promising strategy to ameliorate the treatment of ovarian cancer patients, as the presence of pro-inflammatory tumor infiltrating lymphocytes, especially CD8-positive T cells, correlates with good prognosis and T cells specific for tumor-associated antigens can be isolated from cancer tissue.
  • Cytokine therapy with interleukin-2, interferon-alpha, interferon-gamma or granulocyte- macrophage colony stimulating factor aims at boosting the patient's own anti-tumor immune response and these treatments have already shown promising results in small study cohorts.
  • Monoclonal antibodies that specifically recognize tumor-associated proteins are thought to enhance immune cell-mediated killing of tumor cells.
  • the anti-CA-125 antibodies oregovomab and abagovomab as well as the anti-EpCAM antibody catumaxomab achieved promising results in phase II and III studies.
  • the anti-MUC1 antibody HMFG1 failed to clearly enhance survival in a phase III study.
  • An alternative approach uses monoclonal antibodies to target and block growth factor and survival receptors on tumor cells.
  • trastuzumab anti-HER2/neu antibody
  • MOv18 and MORAb-003 anti-folate receptor alpha antibodies
  • bevacizumab anti-VEGF antibody
  • Adoptive transfer of immune cells achieved heterogeneous results in clinical trials.
  • Adoptive transfer of autologous, in vitro expanded tumor infiltrating T cells was shown to be a promising approach in a pilot trial.
  • transfer of T cells harboring a chimeric antigen receptor specific for folate receptor alpha did not induce a significant clinical response in a phase I trial.
  • Dendritic cells pulsed with tumor cell lysate or tumor- associated proteins in vitro were shown to enhance the anti-tumor T cell response upon transfer, but the extent of T cell activation did not correlate with clinical effects. Transfer of natural killer cells caused significant toxicities in a phase II study.
  • Intrinsic anti-tumor immunity as well as immunotherapy are hampered by an immunosuppressive tumor microenvironment.
  • immunomodulatory drugs like cyclophosphamide, anti-CD25 antibodies and pegylated liposomal doxorubicin are tested in combination with immunotherapy.
  • Most reliable data are currently available for ipilimumab, an anti-CTLA4 antibody, which enhances T cell activity. Ipilimumab was shown to exert significant anti-tumor effects in ovarian cancer patients (Mantia-Smaldone et al., 2012).
  • TAAs tumor associated antigens
  • Cancer-testis antigens The first TAAs ever identified that can be recognized by T cells belong to this class, which was originally called cancer-testis (CT) antigens because of the expression of its members in histologically different human tumors and, among normal tissues, only in spermatocytes/spermatogonia of testis and, occasionally, in placenta. Since the cells of testis do not express class I and II HLA molecules, these antigens cannot be recognized by T cells in normal tissues and can therefore be considered as immunologically tumor-specific.
  • CT antigens are the MAGE family members and NY-ESO-1 .
  • TAAs Differentiation antigens: These TAAs are shared between tumors and the normal tissue from which the tumor arose. Most of the known differentiation antigens are found in melanomas and normal melanocytes. Many of these melanocyte lineage-related proteins are involved in biosynthesis of melanin and are therefore not tumor specific but nevertheless are widely used for cancer immunotherapy. Examples include, but are not limited to, tyrosinase and Melan-A/MART-1 for melanoma or PSA for prostate cancer. c) Over-expressed TAAs: Genes encoding widely expressed TAAs have been detected in histologically different types of tumors as well as in many normal tissues, generally with lower expression levels.
  • TAAs Her-2/neu, survivin, telomerase, or WT1.
  • Tumor-specific antigens arise from mutations of normal genes (such as ⁇ -catenin, CDK4, etc.). Some of these molecular changes are associated with neoplastic transformation and/or progression. Tumor-specific antigens are generally able to induce strong immune responses without bearing the risk for autoimmune reactions against normal tissues. On the other hand, these TAAs are in most cases only relevant to the exact tumor on which they were identified and are usually not shared between many individual tumors. Tumor-specificity (or -association) of a peptide may also arise if the peptide originates from a tumor- (-associated) exon in case of proteins with tumor-specific (-associated) isoforms.
  • TAAs arising from abnormal post-translational modifications may arise from proteins which are neither specific nor overexpressed in tumors but nevertheless become tumor associated by posttranslational processes primarily active in tumors. Examples for this class arise from altered glycosylation patterns leading to novel epitopes in tumors as for MUC1 or events like protein splicing during degradation which may or may not be tumor specific.
  • Oncoviral proteins are viral proteins that may play a critical role in the oncogenic process and, because they are foreign (not of human origin), they can evoke a T-cell response. Examples of such proteins are the human papilloma type 16 virus proteins, E6 and E7, which are expressed in cervical carcinoma.
  • T-cell based immunotherapy targets peptide epitopes derived from tumor-associated or tumor-specific proteins, which are presented by molecules of the major histocompatibility complex (MHC).
  • MHC major histocompatibility complex
  • the antigens that are recognized by the tumor specific T lymphocytes, that is, the epitopes thereof, can be molecules derived from all protein classes, such as enzymes, receptors, transcription factors, etc. which are expressed and, as compared to unaltered cells of the same origin, usually up-regulated in cells of the respective tumor.
  • MHC class I There are two classes of MHC-molecules, MHC class I and MHC class II.
  • MHC class I molecules are composed of an alpha heavy chain and beta-2-microglobulin, MHC class II molecules of an alpha and a beta chain. Their three-dimensional conformation results in a binding groove, which is used for non-covalent interaction with peptides.
  • MHC class I molecules can be found on most nucleated cells. They present peptides that result from proteolytic cleavage of predominantly endogenous proteins, defective ribosomal products (DRIPs) and larger peptides. However, peptides derived from endosomal compartments or exogenous sources are also frequently found on MHC class I molecules. This non-classical way of class I presentation is referred to as cross- presentation in the literature (Brossart and Bevan, 1997; Rock et al., 1990). MHC class II molecules can be found predominantly on professional antigen presenting cells (APCs), and primarily present peptides of exogenous or transmembrane proteins that are taken up by APCs e.g. during endocytosis, and are subsequently processed.
  • APCs professional antigen presenting cells
  • TCR T-cell receptor
  • CD4-positive-helper-T cells bearing the appropriate TCR. It is well known that the TCR, the peptide and the MHC are thereby present in a stoichiometric amount of 1 :1 :1.
  • CD4-positive helper T cells play an important role in inducing and sustaining effective responses by CD8-positive cytotoxic T cells.
  • TAA tumor associated antigens
  • T helper cells support a cytotoxic T cell- (CTL-) friendly cytokine milieu (Mortara et al., 2006) and attract effector cells, e.g. CTLs, natural killer (NK) cells, macrophages, and granulocytes (Hwang et al., 2007).
  • CTL- cytotoxic T cell- friendly cytokine milieu
  • NK natural killer cells
  • macrophages macrophages
  • granulocytes Hwang et al., 2007.
  • MHC class II molecules In the absence of inflammation, expression of MHC class II molecules is mainly restricted to cells of the immune system, especially professional antigen-presenting cells (APC), e.g., monocytes, monocyte-derived cells, macrophages, dendritic cells.
  • APC professional antigen-presenting cells
  • monocytes e.g., monocytes, monocyte-derived cells, macrophages, dendritic cells.
  • monocytes e.g., monocytes, monocyte-derived cells, macrophages, dendritic cells.
  • Elongated (longer) peptides of the invention can act as MHC class II active epitopes.
  • T-helper cells activated by MHC class II epitopes, play an important role in orchestrating the effector function of CTLs in anti-tumor immunity.
  • T-helper cell epitopes that trigger a T-helper cell response of the TH1 type support effector functions of CD8- positive killer T cells, which include cytotoxic functions directed against tumor cells displaying tumor-associated peptide/MHC complexes on their cell surfaces. In this way tumor-associated T-helper cell peptide epitopes, alone or in combination with other tumor-associated peptides, can serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses.
  • CD4-positive T cells are sufficient for inhibiting manifestation of tumors via inhibition of angiogenesis by secretion of interferon-gamma (IFNy) (Beatty and Paterson, 2001 ; Mumberg et al., 1999). There is evidence for CD4 T cells as direct anti-tumor effectors (Braumuller et al., 2013; Tran et al., 2014).
  • IFNy interferon-gamma
  • HLA class II molecules Since the constitutive expression of HLA class II molecules is usually limited to immune cells, the possibility of isolating class II peptides directly from primary tumors was previously not considered possible. However, Dengjel et al. were successful in identifying a number of MHC Class II epitopes directly from tumors (WO 2007/028574, EP 1 760 088 B1 ).
  • CD8 and CD4 dependent Since both types of response, CD8 and CD4 dependent, contribute jointly and synergistically to the anti-tumor effect, the identification and characterization of tumor- associated antigens recognized by either CD8+ T cells (ligand: MHC class I molecule + peptide epitope) or by CD4-positive T-helper cells (ligand: MHC class II molecule + peptide epitope) is important in the development of tumor vaccines.
  • MHC-class-l- binding peptides are usually 8-12 amino acid residues in length and usually contain two conserved residues ("anchors") in their sequence that interact with the corresponding binding groove of the MHC-molecule. In this way, each MHC allele has a "binding motif" determining which peptides can bind specifically to the binding groove.
  • peptides In the MHC class I dependent immune reaction, peptides not only have to be able to bind to certain MHC class I molecules expressed by tumor cells, they subsequently also have to be recognized by T cells bearing specific T cell receptors (TCR).
  • TCR T cell receptors
  • the antigen should be expressed mainly by tumor cells and not, or in comparably small amounts, by normal healthy tissues.
  • the peptide should be over-presented by tumor cells as compared to normal healthy tissues. It is furthermore desirable that the respective antigen is not only present in a type of tumor, but also in high concentrations (i.e. copy numbers of the respective peptide per cell).
  • Tumor- specific and tumor-associated antigens are often derived from proteins directly involved in transformation of a normal cell to a tumor cell due to their function, e.g. in cell cycle control or suppression of apoptosis.
  • downstream targets of the proteins directly causative for a transformation may be up-regulated und thus may be indirectly tumor-associated.
  • Such indirect tumor-associated antigens may also be targets of a vaccination approach (Singh-Jasuja et al., 2004). It is essential that epitopes are present in the amino acid sequence of the antigen, in order to ensure that such a peptide ("immunogenic peptide"), being derived from a tumor associated antigen, leads to an in vitro or in vivo T-cell-response.
  • any peptide able to bind an MHC molecule may function as a T-cell epitope.
  • a prerequisite for the induction of an in vitro or in vivo T-cell-response is the presence of a T cell having a corresponding TCR and the absence of immunological tolerance for this particular epitope. Therefore, TAAs are a starting point for the development of a T cell based therapy including but not limited to tumor vaccines.
  • the methods for identifying and characterizing the TAAs are usually based on the use of T-cells that can be isolated from patients or healthy subjects, or they are based on the generation of differential transcription profiles or differential peptide expression patterns between tumors and normal tissues.
  • the identification of genes over-expressed in tumor tissues or human tumor cell lines, or selectively expressed in such tissues or cell lines, does not provide precise information as to the use of the antigens being transcribed from these genes in an immune therapy. This is because only an individual subpopulation of epitopes of these antigens are suitable for such an application since a T cell with a corresponding TCR has to be present and the immunological tolerance for this particular epitope needs to be absent or minimal. In a very preferred embodiment of the invention it is therefore important to select only those over- or selectively presented peptides against which a functional and/or a proliferating T cell can be found.
  • a functional T cell is defined as a T cell, which upon stimulation with a specific antigen can be clonally expanded and is able to execute effector functions ("effector T cell").
  • the immunogenicity of the underlying peptides is secondary. In these cases, the presentation is the determining factor.
  • the present invention relates to a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 772 or a variant sequence thereof which is at least 77%, preferably at least 88%, homologous (preferably at least 77% or at least 88% identical) to SEQ ID NO: 1 to SEQ ID NO: 772, wherein said variant binds to MHC and/or induces T cells cross-reacting with said peptide, or a pharmaceutical acceptable salt thereof, wherein said peptide is not the underlying full-length polypeptide.
  • the present invention further relates to a peptide of the present invention comprising a sequence that is selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 772 or a variant thereof, which is at least 77%, preferably at least 88%, homologous (preferably at least 77% or at least 88% identical) to SEQ ID NO: 1 to SEQ ID NO: 772, wherein said peptide or variant thereof has an overall length of between 8 and 100, preferably between 8 and 30, and most preferred of between 8 and 14 amino acids.
  • peptides with SEQ ID NO: 1 to SEQ ID NO: 9 bind to HLA-A * 02
  • peptides with SEQ ID NO: 10 to SEQ ID NO: 19 bind to HLA-A *
  • peptides with SEQ ID NO: 20 to SEQ ID NO: 30 bind to HLA-A * 03
  • peptide with SEQ ID NO: 31 binds to HLA-A * 01
  • peptides with SEQ ID NO: 32 to SEQ ID NO: 41 bind to HLA-B * 07
  • peptides with SEQ ID NO: 42 to SEQ ID NO: 51 bind to HLA-B * 08
  • peptides with SEQ ID NO: 52 to SEQ ID NO: 59 bind to HLA-B 4.
  • peptides with SEQ ID NO: 60 to SEQ ID NO: 75 bind to HLA-A * 02
  • peptides with SEQ ID NO: 76 to SEQ ID NO: 82 bind to HLA-A * 24
  • peptides with SEQ ID NO: 83 to SEQ ID NO: 1 1 1 bind to HLA-A * 03
  • peptides with SEQ ID NO: 1 12 to SEQ ID NO: 1 16 bind to HLA-A * 01
  • peptides with SEQ ID NO: 1 17 to SEQ ID NO: 149 bind to HLA-B * 07
  • peptides with SEQ ID NO: 150 to SEQ ID NO: 172 bind to HLA-B * 08
  • peptides with SEQ ID NO: 173 to SEQ ID NO: 215 bind to HLA-B 4.
  • peptides with SEQ ID NO: 216 to SEQ ID NO: 245 bind to HLA-A * 02
  • peptides with SEQ ID NO: 246 to SEQ ID NO: 255 bind to HLA-A * 24
  • peptides with SEQ ID NO: 256 to SEQ ID NO: 287 bind to HLA-A * 03
  • peptides with SEQ ID NO: 288 to SEQ ID NO: 292 bind to HLA-A * 01
  • peptides with SEQ ID NO: 293 to SEQ ID NO: 392 bind to HLA-B * 07
  • peptides with SEQ ID NO: 393 to SEQ ID NO: 395 bind to HLA-B * 08
  • peptides with SEQ ID NO: 396 to SEQ ID NO: 438 bind to HLA- B * 44.
  • peptides with SEQ ID NO: 439 to SEQ ID NO: 551 bind to several HLA class I alleles
  • peptide with SEQ ID NO: 773 binds to HLA-A * 02
  • peptide with SEQ ID NO: 774 binds to HLA-A * 24.
  • peptides with SEQ ID NO: 552 to SEQ ID NO: 772 bind to several HLA class II alleles.
  • Table 1 Peptides according to the present invention
  • PCDHB5 PCDHB15
  • PCDHB9 PCDHB8
  • PCDHB7 PCDHB4
  • PCDHGB7 PCDHGB6, Q9NRJ7, Q9UN66,
  • PCDHGB2 PCDHGB1 , Q9Y5E1 , Q9Y5E2,
  • PCDHGA10 PCDHGA9, Q9Y5E5, Q9Y5E6,
  • PCDHGA5 PCDHGA4, Q9Y5E9, Q9Y5F0,
  • PCDHGA1 PCDHGB8P, Q9Y5F3, Q9Y5F8,
  • PCDHB15 PCDHB14, Q9Y5F9, Q9Y5G0,
  • PCDHB13 PCDHB12, Q9Y5G1 , Q9Y5G2,
  • PCDHB1 1 PCDHB10, Q9Y5G3, Q9Y5G4,
  • PCDHB9 PCDHB8, Q9Y5G5, Q9Y5G6,
  • PCDHB7 PCDHB6, Q9Y5G7, Q9Y5G8,
  • PCDHB4 PCDHB3, Q9Y5G9, Q9Y5H0,
  • PCDHB2 PCDHB16, Q9Y5H1 , Q9Y5H2,
  • CT45A5 CT45A6,
  • TCEA1 P2 TCEA1 .
  • TCEA1 P2 TCEA1 .
  • CTAGE4 CTAGE10P
  • TCEA1 P2 TCEA1 .
  • PCDHB5 PCDHB18, Q96TA0, Q9NRJ7,
  • PCDHB17 PCDHB15, Q9UN66, Q9UN67,
  • PCDHB14 PCDHB1 1 , Q9Y5E1 , Q9Y5E3,
  • PCDHB8 PCDHB6, Q9Y5E6, Q9Y5E7,
  • PCDHB4 PCDHB3, Q9Y5E8, Q9Y5E9,
  • Table 4 HLA Class I peptides according to the present invention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Microbiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Oncology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Hospice & Palliative Care (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Evolutionary Biology (AREA)
  • Medical Informatics (AREA)
  • Spectroscopy & Molecular Physics (AREA)

Abstract

La présente invention concerne des peptides, des protéines, des acides nucléiques et des cellules destinées à être utilisés dans des procédés immunothérapeutiques. En particulier, la présente invention concerne l'immunothérapie du cancer. La présente invention concerne, en outre, des épitopes peptidiques des lymphocytes T associés à une tumeur, seuls ou en combinaison avec d'autres peptides associés à une tumeur, qui peuvent, par exemple, servir de principes pharmaceutiques actifs pour des compositions vaccinales qui stimulent les réponses immunitaires antitumorales, ou pour stimuler des lymphocytes T ex vivo et les transférer aux patients. Des peptides liés aux molécules du complexe majeur d'histocompatibilité (CMH), ou des peptides en tant que tels, peuvent également être des cibles d'anticorps, des récepteurs des lymphocytes T solubles et d'autres molécules de liaison.
PCT/EP2018/051952 2017-01-27 2018-01-26 Nouveaux peptides et combinaison de peptides à utiliser en immunothérapie contre le cancer de l'ovaire et d'autres cancers WO2018138257A1 (fr)

Priority Applications (32)

Application Number Priority Date Filing Date Title
CR20210129A CR20210129A (es) 2017-01-27 2018-01-26 Nuevos péptidos y nuevas combinaciones de péptidos para el uso en la inmunoterapia contra el cáncer de ovario y otros tipos de cáncer (divisional exp. 2019-388)
CN201880008006.XA CN110198734A (zh) 2017-01-27 2018-01-26 用于卵巢癌和其他癌症免疫治疗的新型肽和肽组合物
HRP20230512TT HRP20230512T8 (hr) 2017-01-27 2018-01-26 Novi peptidi i kombinacija peptida za uporabu u imunoterapiji protiv karcinoma jajnika i drugih karcinoma
SG11201906198PA SG11201906198PA (en) 2017-01-27 2018-01-26 Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
EA201991444A EA201991444A1 (ru) 2017-01-27 2018-01-26 Новые пептиды и комбинации пептидов для применения в иммунотерапии рака яичника и других видов рака
MA47367A MA47367B1 (fr) 2017-01-27 2018-01-26 Nouveaux peptides et combinaison de peptides à utiliser en immunothérapie contre le cancer de l'ovaire et d'autres cancers
RS20230396A RS64217B1 (sr) 2017-01-27 2018-01-26 Novi peptidi i kombinacija peptida za upotrebu u imunoterapiji protiv raka jajnika i drugih malignih tumora
JP2019539937A JP7337695B2 (ja) 2017-01-27 2018-01-26 卵巣がんおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチド組み合わせ
MX2019008843A MX2019008843A (es) 2017-01-27 2018-01-26 Peptidos novedosos y combinaciones de peptidos para el uso de la inmunoterapia contra el cancer de ovario y otros tipos de cancer.
CR20190388A CR20190388A (es) 2017-01-27 2018-01-26 Nuevos péptidos y nuevas combinaciones de péptidos para el uso en la inmunoterapia contra el cáncer de ovario y otros tipos de cáncer
AU2018212584A AU2018212584B2 (en) 2017-01-27 2018-01-26 Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
NZ754139A NZ754139A (en) 2017-01-27 2018-01-26 Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
CR20210128A CR20210128A (es) 2017-01-27 2018-01-26 Nuevos péptidos y nuevas combinaciones de péptidos para el uso en la inmunoterapia contra el cáncer de ovario y otros tipos de cancer (divisional exp. 2019-388)
ES18702642T ES2946584T3 (es) 2017-01-27 2018-01-26 Nuevos péptidos y nuevas combinaciones de péptidos para el uso en la inmunoterapia contra el cáncer de ovario y otros tipos de cáncer
EP18702642.2A EP3573647B1 (fr) 2017-01-27 2018-01-26 Nouveaux peptides et combinaison de peptides à utiliser en immunothérapie contre le cancer de l'ovaire et d'autres cancers
SI201830920T SI3573647T1 (sl) 2017-01-27 2018-01-26 Peptidi in kombinacija peptidov za uporabo v imunoterapiji proti raku jajčnikov in drugim oblikam raka
LTEPPCT/EP2018/051952T LT3573647T (lt) 2017-01-27 2018-01-26 Nauji peptidai ir peptidų deriniai, skirti naudoti imunoterapijai prieš kiaušidžių ir kitų tipų vėžį
KR1020197022277A KR20190112271A (ko) 2017-01-27 2018-01-26 난소암 및 다른 암에 대한 면역요법에 사용을 위한 신규 펩티드 및 펩티드의 조합
CR20210130A CR20210130A (es) 2017-01-27 2018-01-26 Nuevos péptidos y nuevas combinaciones de péptidos para el uso en la inmunoterapia contra el cáncer de ovario y otros tipos de càncer (divisional exp. 2019-388)
EP22151693.3A EP4035675A3 (fr) 2017-01-27 2018-01-26 Nouveaux peptides et combinaison de peptides à utiliser en immunothérapie contre le cancer de l'ovaire et d'autres cancers
IL299051A IL299051A (en) 2017-01-27 2018-01-26 New peptides and their combinations for immunotherapy against ovarian cancer and other cancers
BR112019015237A BR112019015237A2 (pt) 2017-01-27 2018-01-26 peptídeos e combinações de peptídeos para uso em imunoterapia contra câncer de ovário e outros cânceres
CA3048108A CA3048108A1 (fr) 2017-01-27 2018-01-26 Nouveaux peptides et combinaison de peptides a utiliser en immunotherapie contre le cancer de l'ovaire et d'autres cancers
PH12019501377A PH12019501377A1 (en) 2017-01-27 2019-06-17 Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
IL268278A IL268278B2 (en) 2017-01-27 2019-07-25 New peptides and their combinations for immunotherapy against ovarian cancer and other cancers
CONC2019/0008008A CO2019008008A2 (es) 2017-01-27 2019-07-25 Nuevos péptidos y nuevas combinaciones de péptidos para el uso en la inmunoterapia contra el cáncer de ovario y otros tipos de cáncer
AU2021201346A AU2021201346A1 (en) 2017-01-27 2021-03-02 Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
AU2021201350A AU2021201350B9 (en) 2017-01-27 2021-03-02 Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
AU2021201349A AU2021201349A1 (en) 2017-01-27 2021-03-02 Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
AU2021201348A AU2021201348A1 (en) 2017-01-27 2021-03-02 Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
AU2021201347A AU2021201347A1 (en) 2017-01-27 2021-03-02 Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
JP2023135232A JP2023179415A (ja) 2017-01-27 2023-08-23 卵巣がんおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチド組み合わせ

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201762451255P 2017-01-27 2017-01-27
US62/451,255 2017-01-27
DE102017101671 2017-01-27
DE102017101671.6 2017-01-27

Related Child Applications (1)

Application Number Title Priority Date Filing Date
EP22151693.3A Previously-Filed-Application EP4035675A3 (fr) 2017-01-27 2018-01-26 Nouveaux peptides et combinaison de peptides à utiliser en immunothérapie contre le cancer de l'ovaire et d'autres cancers

Publications (1)

Publication Number Publication Date
WO2018138257A1 true WO2018138257A1 (fr) 2018-08-02

Family

ID=62978140

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2018/051952 WO2018138257A1 (fr) 2017-01-27 2018-01-26 Nouveaux peptides et combinaison de peptides à utiliser en immunothérapie contre le cancer de l'ovaire et d'autres cancers

Country Status (3)

Country Link
MA (1) MA47367B1 (fr)
TW (1) TWI796314B (fr)
WO (1) WO2018138257A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020048990A1 (fr) * 2018-09-04 2020-03-12 Treos Bio Zrt Vaccins peptidiques
WO2020127546A3 (fr) * 2018-12-18 2020-09-17 Immatics Biotechnologies Gmbh Immunothérapie à l'aide de peptides restreints par b*08 et combinaison de peptides contre des cancers et méthodes associées
US11213578B2 (en) 2017-03-03 2022-01-04 Treos Bio Limited Vaccine
CN113967261A (zh) * 2020-07-24 2022-01-25 中国科学院大连化学物理研究所 Folr1抑制剂的应用和治疗肝癌药物混合物
WO2022225057A1 (fr) * 2021-04-23 2022-10-27 Vlp Therapeutics, Inc. Immunothérapie ciblant la galectine
EP3990483A4 (fr) * 2019-06-25 2024-02-21 Université de Montréal Nouveaux antigènes spécifiques à une tumeur pour le cancer de l'ovaire

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115350145A (zh) * 2022-09-06 2022-11-18 华中科技大学同济医学院附属协和医院 细菌介导负载二甲双胍的多肽水凝胶在肿瘤免疫治疗中的应用

Citations (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4342566A (en) 1980-02-22 1982-08-03 Scripps Clinic & Research Foundation Solid phase anti-C3 assay for detection of immune complexes
US4440859A (en) 1977-05-27 1984-04-03 The Regents Of The University Of California Method for producing recombinant bacterial plasmids containing the coding sequences of higher organisms
US4530901A (en) 1980-01-08 1985-07-23 Biogen N.V. Recombinant DNA molecules and their use in producing human interferon-like polypeptides
US4582800A (en) 1982-07-12 1986-04-15 Hoffmann-La Roche Inc. Novel vectors and method for controlling interferon expression
US4677063A (en) 1985-05-02 1987-06-30 Cetus Corporation Human tumor necrosis factor
US4678751A (en) 1981-09-25 1987-07-07 Genentech, Inc. Hybrid human leukocyte interferons
US4704362A (en) 1977-11-08 1987-11-03 Genentech, Inc. Recombinant cloning vehicle microbial polypeptide expression
US4710463A (en) 1978-12-22 1987-12-01 Biogen N.V. Recombinant DNA molecules capable of expressing HBV core and surface antigens
US4757006A (en) 1983-10-28 1988-07-12 Genetics Institute, Inc. Human factor VIII:C gene and recombinant methods for production
US4766075A (en) 1982-07-14 1988-08-23 Genentech, Inc. Human tissue plasminogen activator
US4810648A (en) 1986-01-08 1989-03-07 Rhone Poulenc Agrochimie Haloarylnitrile degrading gene, its use, and cells containing the gene
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4897445A (en) 1986-06-27 1990-01-30 The Administrators Of The Tulane Educational Fund Method for synthesizing a peptide containing a non-peptide bond
WO1994029348A2 (fr) 1993-06-03 1994-12-22 Therapeutic Antibodies Inc. Production de fragments d'anticorps
WO1995018145A1 (fr) 1993-12-24 1995-07-06 Ilexus Pty Ltd Conjugues de mucine humaine et d'un polymere d'hydrate de carbone ainsi que leur utilisation dans le traitement du cancer
WO1997026328A1 (fr) 1996-01-17 1997-07-24 Imperial College Innovations Limited Immunotherapie utilisant des lymphocytes t cytotoxiques (ctl)
US5849589A (en) 1996-03-11 1998-12-15 Duke University Culturing monocytes with IL-4, TNF-α and GM-CSF TO induce differentiation to dendric cells
WO2001072768A2 (fr) 2000-03-27 2001-10-04 Technion Research And Development Foundation Ltd. Complexes majeurs d'histocompatibilite monocatenaires de classe 1, constructions les codant et leurs methodes de production
US6406705B1 (en) 1997-03-10 2002-06-18 University Of Iowa Research Foundation Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant
WO2003014151A2 (fr) * 2001-08-10 2003-02-20 Genset S.A. Adn complementaire et proteines humains et leurs utilisations
WO2003068201A2 (fr) 2002-02-13 2003-08-21 Technion Research & Development Foundation Ltd. Anticorps presentant une specifite de type recepteur des lymphocytes t, une affinite encore superieure, et utilisation de celui-ci dans la detection et le traitement du cancer, d'infections virales et de maladies auto-immunes
WO2003070752A2 (fr) 2002-02-20 2003-08-28 Dyax Corporation Ligands de liaison au complexe mhc-peptide
WO2004033685A1 (fr) 2002-10-09 2004-04-22 Avidex Ltd Recepteurs de lymphocytes t de recombinaison a chaine unique
WO2004074322A1 (fr) 2003-02-22 2004-09-02 Avidex Ltd Recepteur des lymphocytes t soluble modifie
WO2004084798A2 (fr) 2003-03-26 2004-10-07 Technion Research & Development Foundation Ltd. Compositions de liaison avec un complexe a antigene, et utilisations
WO2005017102A2 (fr) * 2003-05-30 2005-02-24 Diadexus, Inc. Compositions, variants d'epissage et procedes associes a des acides nucleiques et des proteines specifiques
WO2005049073A2 (fr) * 2003-11-19 2005-06-02 Survac Aps Proteines appartenant a la famille bcl-2, fragments associes, et utilisation therapeutique de ces proteines et fragments sur des patients atteints du cancer
WO2007028574A2 (fr) 2005-09-05 2007-03-15 Immatics Biotechnologies Gmbh Peptides associes aux tumeurs qui se lient etroitement aux molecules du systeme majeur d'histocompatibilite humain (hla) de la classe ii
WO2009015842A2 (fr) * 2007-07-27 2009-02-05 Immatics Biotechnologies Gmbh Nouveaux épitopes immunogènes destinés à l'immunothérapie
EP2111867A1 (fr) * 2008-04-24 2009-10-28 Immatics Biotechnologies GmbH Nouvelles formules de peptides associées aux tumeurs à liaison aux molécules II ou I de classe d'antigène (HLA) de leucocyte humain pour vaccins
EP2112253A2 (fr) 2008-04-21 2009-10-28 United Technologies Corporation Procédé de rétablissement d'un article
WO2009143843A1 (fr) * 2008-04-17 2009-12-03 Herlev Hospital Immunothérapie à base d'indoléamine 2,3-dioxygénase
WO2010037395A2 (fr) * 2008-10-01 2010-04-08 Dako Denmark A/S Multimères de mhc dans des vaccins et la surveillance immunitaire contre le cancer
WO2010037397A1 (fr) * 2008-10-01 2010-04-08 Dako Denmark A/S Multimères de mhc dans la surveillance immunitaire contre le cmv
US20100113300A1 (en) 2002-11-09 2010-05-06 Immunocore Limited T cell receptor display
WO2011128448A1 (fr) * 2010-04-16 2011-10-20 Immatics Biotechnologies Gmbh Différenciation quantitative de peptides à restriction hla traités naturellement dans le but de développer une immunothérapie pour les cancers, les maladies auto-immunes et les maladies infectieuses
WO2012056407A1 (fr) 2010-10-26 2012-05-03 Technion Research & Development Foundation Ltd. Anticorps qui se lient à des ligands de récepteurs de lymphocytes t solubles
WO2013057586A1 (fr) 2011-10-19 2013-04-25 Oslo Universitetssykehus Hf Compositions et procédés de production de récepteurs solubles des lymphocytes t
US20130115191A1 (en) 2000-06-05 2013-05-09 Altor Bioscience Corporation T cell receptor fusions and conjugates and methods of use thereof
WO2014071978A1 (fr) 2012-11-08 2014-05-15 Roche Diagnostics Gmbh Acides nucléiques codant pour des polypeptides chimériques pour criblage de banque
WO2014191359A1 (fr) 2013-05-28 2014-12-04 Rheinische Friedrich-Wilhelms Universität Bonn Aptamères et utilisation d'aptamères dans le diagnostic et le traitement du cancer
WO2015063302A2 (fr) * 2013-11-04 2015-05-07 Immatics Biotechnologies Gmbh Immunothérapie personnalisée contre plusieurs tumeurs neuronales et cérébrales
WO2017009400A1 (fr) * 2015-07-15 2017-01-19 Immatics Biotechnologies Gmbh Nouveaux peptides et combinaison de peptides destinés à être utilisés en immunothérapie contre le cancer ovarien épithélial et d'autres cancers

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201505305D0 (en) * 2015-03-27 2015-05-13 Immatics Biotechnologies Gmbh Novel Peptides and combination of peptides for use in immunotherapy against various tumors

Patent Citations (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4440859A (en) 1977-05-27 1984-04-03 The Regents Of The University Of California Method for producing recombinant bacterial plasmids containing the coding sequences of higher organisms
US4704362A (en) 1977-11-08 1987-11-03 Genentech, Inc. Recombinant cloning vehicle microbial polypeptide expression
US4710463A (en) 1978-12-22 1987-12-01 Biogen N.V. Recombinant DNA molecules capable of expressing HBV core and surface antigens
US4530901A (en) 1980-01-08 1985-07-23 Biogen N.V. Recombinant DNA molecules and their use in producing human interferon-like polypeptides
US4342566A (en) 1980-02-22 1982-08-03 Scripps Clinic & Research Foundation Solid phase anti-C3 assay for detection of immune complexes
US4678751A (en) 1981-09-25 1987-07-07 Genentech, Inc. Hybrid human leukocyte interferons
US4582800A (en) 1982-07-12 1986-04-15 Hoffmann-La Roche Inc. Novel vectors and method for controlling interferon expression
US4766075A (en) 1982-07-14 1988-08-23 Genentech, Inc. Human tissue plasminogen activator
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4757006A (en) 1983-10-28 1988-07-12 Genetics Institute, Inc. Human factor VIII:C gene and recombinant methods for production
US4677063A (en) 1985-05-02 1987-06-30 Cetus Corporation Human tumor necrosis factor
US4810648A (en) 1986-01-08 1989-03-07 Rhone Poulenc Agrochimie Haloarylnitrile degrading gene, its use, and cells containing the gene
US4897445A (en) 1986-06-27 1990-01-30 The Administrators Of The Tulane Educational Fund Method for synthesizing a peptide containing a non-peptide bond
WO1994029348A2 (fr) 1993-06-03 1994-12-22 Therapeutic Antibodies Inc. Production de fragments d'anticorps
WO1995018145A1 (fr) 1993-12-24 1995-07-06 Ilexus Pty Ltd Conjugues de mucine humaine et d'un polymere d'hydrate de carbone ainsi que leur utilisation dans le traitement du cancer
WO1997026328A1 (fr) 1996-01-17 1997-07-24 Imperial College Innovations Limited Immunotherapie utilisant des lymphocytes t cytotoxiques (ctl)
US5849589A (en) 1996-03-11 1998-12-15 Duke University Culturing monocytes with IL-4, TNF-α and GM-CSF TO induce differentiation to dendric cells
US6406705B1 (en) 1997-03-10 2002-06-18 University Of Iowa Research Foundation Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant
WO2001072768A2 (fr) 2000-03-27 2001-10-04 Technion Research And Development Foundation Ltd. Complexes majeurs d'histocompatibilite monocatenaires de classe 1, constructions les codant et leurs methodes de production
US20130115191A1 (en) 2000-06-05 2013-05-09 Altor Bioscience Corporation T cell receptor fusions and conjugates and methods of use thereof
WO2003014151A2 (fr) * 2001-08-10 2003-02-20 Genset S.A. Adn complementaire et proteines humains et leurs utilisations
WO2003068201A2 (fr) 2002-02-13 2003-08-21 Technion Research & Development Foundation Ltd. Anticorps presentant une specifite de type recepteur des lymphocytes t, une affinite encore superieure, et utilisation de celui-ci dans la detection et le traitement du cancer, d'infections virales et de maladies auto-immunes
WO2003070752A2 (fr) 2002-02-20 2003-08-28 Dyax Corporation Ligands de liaison au complexe mhc-peptide
WO2004033685A1 (fr) 2002-10-09 2004-04-22 Avidex Ltd Recepteurs de lymphocytes t de recombinaison a chaine unique
US20100113300A1 (en) 2002-11-09 2010-05-06 Immunocore Limited T cell receptor display
WO2004074322A1 (fr) 2003-02-22 2004-09-02 Avidex Ltd Recepteur des lymphocytes t soluble modifie
WO2004084798A2 (fr) 2003-03-26 2004-10-07 Technion Research & Development Foundation Ltd. Compositions de liaison avec un complexe a antigene, et utilisations
WO2005017102A2 (fr) * 2003-05-30 2005-02-24 Diadexus, Inc. Compositions, variants d'epissage et procedes associes a des acides nucleiques et des proteines specifiques
WO2005049073A2 (fr) * 2003-11-19 2005-06-02 Survac Aps Proteines appartenant a la famille bcl-2, fragments associes, et utilisation therapeutique de ces proteines et fragments sur des patients atteints du cancer
WO2007028574A2 (fr) 2005-09-05 2007-03-15 Immatics Biotechnologies Gmbh Peptides associes aux tumeurs qui se lient etroitement aux molecules du systeme majeur d'histocompatibilite humain (hla) de la classe ii
WO2009015842A2 (fr) * 2007-07-27 2009-02-05 Immatics Biotechnologies Gmbh Nouveaux épitopes immunogènes destinés à l'immunothérapie
WO2009143843A1 (fr) * 2008-04-17 2009-12-03 Herlev Hospital Immunothérapie à base d'indoléamine 2,3-dioxygénase
EP2112253A2 (fr) 2008-04-21 2009-10-28 United Technologies Corporation Procédé de rétablissement d'un article
EP2111867A1 (fr) * 2008-04-24 2009-10-28 Immatics Biotechnologies GmbH Nouvelles formules de peptides associées aux tumeurs à liaison aux molécules II ou I de classe d'antigène (HLA) de leucocyte humain pour vaccins
WO2010037395A2 (fr) * 2008-10-01 2010-04-08 Dako Denmark A/S Multimères de mhc dans des vaccins et la surveillance immunitaire contre le cancer
WO2010037397A1 (fr) * 2008-10-01 2010-04-08 Dako Denmark A/S Multimères de mhc dans la surveillance immunitaire contre le cmv
WO2011128448A1 (fr) * 2010-04-16 2011-10-20 Immatics Biotechnologies Gmbh Différenciation quantitative de peptides à restriction hla traités naturellement dans le but de développer une immunothérapie pour les cancers, les maladies auto-immunes et les maladies infectieuses
US20130096016A1 (en) 2010-04-16 2013-04-18 Immatics Biotechnologies Gmbh Method for differentially quantifying naturally processed hla-restricted peptides for cancer, autoimmune and infectious diseases immunotherapy development
WO2012056407A1 (fr) 2010-10-26 2012-05-03 Technion Research & Development Foundation Ltd. Anticorps qui se lient à des ligands de récepteurs de lymphocytes t solubles
WO2013057586A1 (fr) 2011-10-19 2013-04-25 Oslo Universitetssykehus Hf Compositions et procédés de production de récepteurs solubles des lymphocytes t
WO2014071978A1 (fr) 2012-11-08 2014-05-15 Roche Diagnostics Gmbh Acides nucléiques codant pour des polypeptides chimériques pour criblage de banque
WO2014191359A1 (fr) 2013-05-28 2014-12-04 Rheinische Friedrich-Wilhelms Universität Bonn Aptamères et utilisation d'aptamères dans le diagnostic et le traitement du cancer
WO2015063302A2 (fr) * 2013-11-04 2015-05-07 Immatics Biotechnologies Gmbh Immunothérapie personnalisée contre plusieurs tumeurs neuronales et cérébrales
WO2017009400A1 (fr) * 2015-07-15 2017-01-19 Immatics Biotechnologies Gmbh Nouveaux peptides et combinaison de peptides destinés à être utilisés en immunothérapie contre le cancer ovarien épithélial et d'autres cancers

Non-Patent Citations (501)

* Cited by examiner, † Cited by third party
Title
"GenBank", Database accession no. X00497
"RefSeq, The NCBI handbook", 2002
"The Molecular Taxonomy of Primary Prostate Cancer", CELL, vol. 163, 2015, pages 1011 - 1025
ABBA, M. C. ET AL., MOL.CANCER RES, vol. 5, 2007, pages 881 - 890
ABDELMALAK, C. A. ET AL., CLIN LAB, vol. 60, 2014, pages 55 - 61
ABE, A. ET AL., GENES CHROMOSOMES.CANCER, vol. 55, 2016, pages 242 - 250
AGHAJANOVA, L. ET AL., HUM.REPROD., vol. 30, 2015, pages 232 - 238
AGHERBI, H. ET AL., PLOS.ONE, vol. 4, 2009, pages e5622
AGUILO, F. ET AL., CURR.TOP.MICROBIOL.LMMUNOL., vol. 394, 2016, pages 29 - 39
AKAGI, T. ET AL., J BIOL CHEM, vol. 290, 2015, pages 22460 - 22473
AL, ZEYADI M. ET AL., BIOTECHNOL.BIOTECHNOL.EQUIP., vol. 29, 2015, pages 111 - 118
ALBERGARIA, A. ET AL., INT.J DEV.BIOL, vol. 55, 2011, pages 811 - 822
ALENTORN, A. ET AL., PRESSE MED, vol. 42, 2013, pages 806 - 813
ALHOSIN, M. ET AL., J EXP.CLIN CANCER RES, vol. 35, 2016, pages 174
ALLISON, J. P ET AL., SCIENCE, vol. 270, 1995, pages 932 - 933
ALRAWI, S. J. ET AL., ANTICANCER RES, vol. 26, 2006, pages 107 - 119
ALVARADO-RUIZ, L. ET AL., ASIAN PAC.J CANCER PREV., vol. 17, 2016, pages 1037 - 1047
ALZRIGAT, M. ET AL., ONCOTARGET, 2016
AMSTERDAM, A. ET AL., ACTA HISTOCHEM., vol. 116, 2014, pages 781 - 787
ANDERSEN, R. S. ET AL., NAT.PROTOC., vol. 7, 2012, pages 891 - 902
ANDRADE, V. C. ET AL., CANCER IMMUN., vol. 8, 2008, pages 2
ANDRADE, V. C. ET AL., EXP.HEMATOL., vol. 37, 2009, pages 446 - 449
ANGELOPOULOU, K. ET AL., MAMM.GENOME, vol. 21, 2010, pages 516 - 524
ANGULO, J. C. ET AL., J UROL., vol. 195, 2016, pages 619 - 626
ANSARI, K. I. ET AL., J MOL.ENDOCRINOL., vol. 48, 2012, pages 61 - 75
APPAY, V. ET AL., EUR.J IMMUNOL., vol. 36, 2006, pages 1805 - 1814
APRELIKOVA, O. ET AL., CANCER RES, vol. 69, 2009, pages 616 - 624
ARSENIC, R. ET AL., BMC.CANCER, vol. 15, 2015, pages 784
ASKEW, E. B. ET AL., J BIOL CHEM, vol. 284, 2009, pages 34793 - 34808
AUNG, P. P. ET AL., ONCOGENE, vol. 25, 2006, pages 2546 - 2557
AVASARALA, S. ET AL., BIOL OPEN., vol. 2, 2013, pages 675 - 685
AVGUSTINOVA, A. ET AL., NAT COMMUN., vol. 7, 2016, pages 10305
AYTES, A. ET AL., PROC.NATL.ACAD.SCI.U.S.A, vol. 110, 2013, pages E3506 - E3515
BAHNASSY, A. A. ET AL., WORLD J GASTROENTEROL., vol. 20, 2014, pages 18240 - 18248
BAILEY, V. ET AL., METHODS, vol. 52, 2010, pages 237 - 241
BALAZ, P. ET AL., ANN.SURG., vol. 235, 2002, pages 519 - 527
BANCHEREAU, J. ET AL., CELL, vol. 106, 2001, pages 271 - 274
BAND, A. M. ET AL., J MAMMARY.GLAND.BIOL NEOPLASIA., vol. 16, 2011, pages 109 - 115
BAO, L. ET AL., CELL BIOL TOXICOL., vol. 32, 2016, pages 419 - 435
BAROY, T. ET AL., MOL.CANCER, vol. 13, 2014, pages 93
BARTOLINI, A. ET AL., CLIN CANCER RES, vol. 22, 2016, pages 4923 - 4933
BATY, F. ET AL., J BIOMED.LNFORM., vol. 58, 2015, pages 175 - 185
BEARD, R. E. ET AL., CLIN CANCER RES, vol. 19, 2013, pages 4941 - 4950
BEATTY, G. ET AL., J IMMUNOL, vol. 166, 2001, pages 2276 - 2282
BEGGS, J. D., NATURE, vol. 275, 1978, pages 104 - 109
BEKE, L. ET AL., BIOSCI.REP., vol. 35, 2015
BELL, J. L. ET AL., CELL MOL LIFE SCI., vol. 70, 2013, pages 2657 - 2675
BELL, J. L. ET AL., J CLIN ONCOL, vol. 33, 2015, pages 1285 - 1293
BENZ, C. C. ET AL., ONCOGENE, vol. 15, 1997, pages 1513 - 1525
BERGAMINI, A. ET AL., EXPERT.OPIN.LNVESTIG.DRUGS, vol. 25, 2016, pages 1405 - 1412
BERGER, C. ET AL., CURR.MOL.MED., vol. 13, 2013, pages 1229 - 1240
BERNSTEIN, M. B. ET AL., CANCER BIOTHER.RADIOPHARM., vol. 29, 2014, pages 153 - 161
BEYRANVAND, NEJAD E. ET AL., CANCER RES, vol. 76, 2016, pages 6017 - 6029
BHAN, S. ET AL., ONCOL REP., vol. 28, 2012, pages 1498 - 1502
BIERKENS, M. ET AL., GENES CHROMOSOMES.CANCER, vol. 52, 2013, pages 56 - 68
BIKKAVILLI, R. K. ET AL., ONCOGENE, vol. 34, 2015, pages 5317 - 5328
BISIG, B. ET AL., BEST.PRACT.RES CLIN HAEMATOL., vol. 25, 2012, pages 13 - 28
BODE, P. K. ET AL., MOD.PATHOL., vol. 27, 2014, pages 899 - 905
BOEVA, V. ET AL., PLOS.ONE, vol. 8, 2013, pages e72182
BOGUSH, T. A. ET AL., ANTIBIOT.KHIMIOTER., vol. 54, 2009, pages 41 - 49
BONITSIS, N. ET AL., EXP.ONCOL, vol. 28, 2006, pages 187 - 193
BORGONO, C. A. ET AL., CANCER RES, vol. 63, 2003, pages 9032 - 9041
BORGONO, C. A. ET AL., CLIN CANCER RES, vol. 12, 2006, pages 1487 - 1493
BORGONO, C. A. ET AL., J BIOL CHEM, vol. 282, 2007, pages 2405 - 2422
BOROWICZ, S. ET AL., J VIS.EXP., 2014, pages e51998
BOULTER, J. M. ET AL., PROTEIN ENG, vol. 16, 2003, pages 707 - 711
BRAUMULLER, H. ET AL., NATURE, 2013
BRINKMANN, U. ET AL., PROC.NATL.ACAD.SCI.U.S.A, vol. 95, 1998, pages 10757 - 10762
BROSSART, P. ET AL., BLOOD, vol. 90, 1997, pages 1594 - 1599
BRUCKDORFER, T. ET AL., CURR.PHARM.BIOTECHNOL., vol. 5, 2004, pages 29 - 43
BRUEY, J. M. ET AL., J BIOL CHEM, vol. 279, 2004, pages 51897 - 51907
BRYAN, R. T. ET AL., J UROL., vol. 184, 2010, pages 423 - 431
BRYAN, R. T., PHILOS.TRANS.R SOC.LOND B BIOL SCI., vol. 370, 2015, pages 20140042
BUCHET-POYAU, K. ET AL., NUCLEIC ACIDS RES, vol. 35, 2007, pages 1289 - 1300
BUNDELA, S. ET AL., PLOS.ONE, vol. 9, 2014, pages e102610
BURNETT, R. M. ET AL., ONCOTARGET., vol. 6, 2015, pages 12682 - 12696
CANO, A. ET AL., FUTURE.ONCOL, vol. 8, 2012, pages 1095 - 1108
CAPUTI, F. F. ET AL., J MOL.NEUROSCI., vol. 51, 2013, pages 532 - 538
CARD, K. F. ET AL., CANCER IMMUNOL IMMUNOTHER., vol. 53, 2004, pages 345 - 357
CARRERA, M. ET AL., INT.J CLIN EXP.PATHOL., vol. 8, 2015, pages 3613 - 3623
CERVEIRA, N. ET AL., BMC.CANCER, vol. 10, 2010, pages 518
CHAKRABARTY, S. ET AL., J CELL PHYSIOL, vol. 186, 2001, pages 47 - 52
CHAN, M. H. ET AL., PEDIATR.BLOOD CANCER, vol. 59, 2012, pages 1173 - 1179
CHANDRA, V. ET AL., CELL DEATH.DIS., vol. 5, 2014
CHANG, H. ET AL., BIOCHEM.BIOPHYS.RES COMMUN., vol. 464, 2015, pages 45 - 50
CHANG, Q. ET AL., ONCOTARGET, vol. 6, 2015, pages 42838 - 42853
CHEN, H. S. ET AL., HONGHUA GAN ZANG.BING.ZA ZHI., vol. 11, 2003, pages 145 - 148
CHEN, S. T. ET AL., CANCER SCI., vol. 102, 2011, pages 2191 - 2198
CHEN, Y. C. ET AL., TAIWAN.J OBSTET.GYNECOL., vol. 54, 2015, pages 572 - 579
CHEN, Y. ET AL., CANCER BIOL THER., vol. 11, 2011, pages 497 - 511
CHEN, Y. ET AL., ONCO.TARGETS.THER., vol. 7, 2014, pages 1465 - 1472
CHEN, Y. L. ET AL., INT J SURG., vol. 11, 2013, pages 85 - 91
CHEN, Y. T. ET AL., INT.J CANCER, vol. 124, 2009, pages 2893 - 2898
CHEN, Y. T. ET AL., PROC.NATL.ACAD.SCI.U.S.A, vol. 102, 2005, pages 7940 - 7945
CHENG, Y. C. ET AL., J NEUROCHEM., vol. 110, 2009, pages 947 - 955
CHEUNG, A. ET AL., ONCOTARGET., vol. 7, 2016, pages 52553 - 52574
CHEVILLARD, G. ET AL., BLOOD, vol. 117, 2011, pages 2005 - 2008
CHOI, M. R. ET AL., APMIS, vol. 123, 2015, pages 65 - 71
CHOIJAMTS, B. ET AL., STEM CELLS, vol. 29, 2011, pages 1485 - 1495
CHUNG, H. ET AL., BIOL CHEM, vol. 393, 2012, pages 413 - 420
CHUNG, S. ET AL., ONCOTARGET, vol. 3, 2012, pages 1629 - 1640
CIRUELOS GIL, E. M., CANCER TREAT.REV, vol. 40, 2014, pages 862 - 871
CLANCY, A. A. ET AL., ANN.ONCOL, vol. 27, 2016, pages 1696 - 1705
CLERMONT, P. L. ET AL., BR.J CANCER, vol. 111, 2014, pages 1663 - 1672
CLERMONT, P. L. ET AL., CLIN EPIGENETICS, vol. 7, 2015, pages 40
CLERMONT, P. L. ET AL., CLIN EPIGENETICS, vol. 8, 2016, pages 16
COHEN, C. J. ET AL., J IMMUNOL, vol. 170, 2003, pages 4349 - 4361
COHEN, C. J. ET AL., J MOL RECOGNIT, vol. 16, 2003, pages 324 - 332
COHEN, S. N. ET AL., PROC.NATL.ACAD.SCI.U.S.A, vol. 69, 1972, pages 2110 - 2114
COLAS, E. ET AL., CLIN TRANSL.ONCOL, vol. 14, 2012, pages 715 - 720
COLIGAN ET AL.: "Current Protocols In Protein Science", 1995, JOHN WILEY AND SONS
COLIGAN, J. E. ET AL., CURRENT PROTOCOLS IN PROTEIN SCIENCE, 1995
COLOMBETTI, S. ET AL., J IMMUNOL., vol. 176, 2006, pages 2730 - 2738
COLOVAI, A. I. ET AL., CYTOMETRY B CLIN CYTOM., vol. 72, 2007, pages 354 - 362
CORTESINI, R., JOP, vol. 8, 2007, pages 697 - 703
COULIE, P. G. ET AL., IMMUNOL.REV, vol. 188, 2002, pages 33 - 42
COUTTE, L. ET AL., GENE, vol. 240, 1999, pages 201 - 207
CUI, X. P. ET AL., DIG.DIS.SCI., vol. 59, 2014, pages 1442 - 1451
CURRAN, K. J. ET AL., MOL.THER., vol. 23, 2015, pages 769 - 778
DAI, W. ET AL., CANCER RES, vol. 5, 2015, pages 2697 - 2707
DALERBA, P. ET AL., INT.J CANCER, vol. 93, 2001, pages 85 - 90
DANNENMANN, S. R. ET AL., CANCER IMMUNOL.RES., vol. 1, 2013, pages 288 - 295
DARDA, L. ET AL., PLOS.ONE, vol. 10, 2015, pages e0122285
DARLING, M. R. ET AL., HEAD NECK PATHOL., vol. 2, 2008, pages 169 - 174
DAT, LE T. ET AL., INT.J ONCOL, vol. 40, 2012, pages 1455 - 1469
DAVIDSON, B. ET AL., J CELL MOL.MED., vol. 15, 2011, pages 535 - 544
DAVIS, M. P., CLEVE.CLIN J MED, vol. 79, no. 1, 2012, pages eS51 - eS55
DE GOEJE, P. L. ET AL., ONCOIMMUNOLOGY, vol. 4, 2015, pages e1014242
DE MATOS, SIMOES R. ET AL., BMC.SYST.BIOL, vol. 9, 2015, pages 21
DE, MEULENAERE A. ET AL., PATHOBIOLOGY, vol. 83, 2016, pages 327 - 333
DE, PLAEN E. ET AL., IMMUNOGENETICS, vol. 40, 1994, pages 360 - 369
DENGJEL, J. ET AL., CLIN CANCER RES, vol. 12, 2006, pages 4163 - 4170
DENKBERG, G. ET AL., J IMMUNOL, vol. 171, 2003, pages 2197 - 2207
DEVETZI, M. ET AL., THROMB.HAEMOST., vol. 109, 2013, pages 716 - 725
DEWAR, R. ET AL., ARCH.PATHOL.LAB MED, vol. 135, 2011, pages 422 - 429
DIAS, R. P. ET AL., EPIGENOMICS., vol. 5, 2013, pages 331 - 340
DOBROWOLSKA, H. ET AL., CYTOMETRY B CLIN CYTOM., vol. 84, 2013, pages 21 - 29
DONG, Q. ET AL., BIOMED.RES INT., vol. 2015, 2015, pages 156432
DORN, J. ET AL., CRIT REV CLIN LAB SCI., vol. 51, 2014, pages 63 - 84
DU, T. ET AL., MOL.CANCER, vol. 13, 2014, pages 100
DUA, P. ET AL., CANCER RES, vol. 73, 2013, pages 1934 - 1945
DUAN, Z. ET AL., CLIN CANCER RES, vol. 9, 2003, pages 2778 - 2785
DUFOUR, C. ET AL., CANCER, vol. 118, 2012, pages 3812 - 3821
DYRSKJOT, L. ET AL., BR.J CANCER, vol. 107, 2012, pages 116 - 122
EK, S. ET AL., CANCER RES, vol. 62, 2002, pages 4398 - 4405
EMMRICH, S. ET AL., GENES DEV., vol. 28, 2014, pages 858 - 874
FABBRI, C. ET AL., DIG.ENDOSC., 2017
FALK, K. ET AL., NATURE, vol. 351, 1991, pages 290 - 296
FAN, M. ET AL., INT.J CLIN EXP.PATHOL., vol. 7, 2014, pages 6768 - 6775
FANG, F. ET AL., CLIN CANCER RES, vol. 20, 2014, pages 6504 - 6516
FANG, L. ET AL., BIOCHEM.BIOPHYS.RES COMMUN., vol. 446, 2014, pages 272 - 279
FAURE, A. ET AL., NAT REV UROL., vol. 13, 2016, pages 141 - 150
FENG, X. ET AL., MOL.BIOSYST., vol. 11, 2015, pages 2946 - 2954
FERRE, H. ET AL., PROTEIN SCI., vol. 12, 2003, pages 551 - 559
FINDEIS-HOSEY, J. J. ET AL., BIOTECH.HISTOCHEM., vol. 87, 2012, pages 24 - 29
FISHMAN, W. H., TUMOUR.BIOL, vol. 16, 1995, pages 394 - 402
FOLLENZI, A. ET AL., NAT GENET., vol. 25, 2000, pages 217 - 222
FONG, L. ET AL., PROC.NATL.ACAD.SCI.U.S.A, vol. 98, 2001, pages 8809 - 8814
FONTALBA, A. ET AL., J IMMUNOL., vol. 179, 2007, pages 8519 - 8524
FORGHANIFARD, M. M. ET AL., CANCER BIOL THER., vol. 12, 2011, pages 191 - 197
FRASOR, J. ET AL., MOL.CELL ENDOCRINOL., vol. 418 Pt 3, 2015, pages 235 - 239
FRITZSCHE, F. ET AL., BR.J CANCER, vol. 94, 2006, pages 540 - 547
FRY, E. A. ET AL., INT.J CANCER, vol. 140, 2017, pages 495 - 503
FUJIYAMA, T. ET AL., J DERMATOL.SCI., vol. 75, 2014, pages 43 - 48
FUKUMOTO, I. ET AL., J HUM.GENET., vol. 61, 2016, pages 109 - 118
FUQUA, S. A. ET AL., BREAST CANCER RES TREAT., vol. 144, 2014, pages 11 - 19
GABRILOVICH, D. I. ET AL., NAT MED., vol. 2, 1996, pages 1096 - 1103
GAN, X. ET AL., DIS.MARKERS, vol. 2016, 2016, pages 5259602
GANGULY, R. ET AL., MOL.CANCER THER., vol. 13, 2014, pages 1393 - 1398
GARG, M. ET AL., J CLIN ENDOCRINOL.METAB, vol. 99, 2014, pages E62 - E72
GATTINONI, L. ET AL., NAT REV.LMMUNOL, vol. 6, 2006, pages 383 - 393
GE, L. ET AL., EUR.REV MED PHARMACOL.SCI., vol. 19, 2015, pages 2703 - 2710
GE, L. ET AL., J BIOMED.RES, vol. 29, 2015
GEYER, C. R., EPIGENETICS, vol. 5, 2010, pages 696 - 703
GHODSI, M. ET AL., INT.J SURG., vol. 13, 2015, pages 193 - 197
GIBBS, P. ET AL., MELANOMA RES, vol. 10, 2000, pages 259 - 264
GLEIZE, V. ET AL., ANN.NEUROL., vol. 78, 2015, pages 355 - 374
GNJATIC, S. ET AL., PROC NATL.ACAD.SCI.U.S.A, vol. 100, 2003, pages 8862 - 8867
GODKIN, A. ET AL., INT.LMMUNOL, vol. 9, 1997, pages 905 - 911
GOMEZ, A. ET AL., MOL.PHARMACOL., vol. 78, 2010, pages 1004 - 1011
GONG, Y. ET AL., ADV.ANAT.PATHOL., vol. 21, 2014, pages 191 - 200
GOTTLIEB, H. B. ET AL., J NEUROENDOCRINOL., vol. 19, 2007, pages 531 - 542
GRAGERT, L. ET AL., HUM.LMMUNOL., vol. 74, 2013, pages 1313 - 1320
GRAH, J. J. ET AL., TUMORI, vol. 100, 2014, pages 60 - 68
GRATIO, V. ET AL., AM.J PATHOL., vol. 179, 2011, pages 2625 - 2636
GREEN, M. R. ET AL., MOLECULAR CLONING, A LABORATORY MANUAL 4TH, 2012
GREENFIELD, E. A., ANTIBODIES: A LABORATORY MANUAL 2ND, 2014
GU, C. ET AL., STEM CELLS, vol. 31, 2013, pages 870 - 881
GU, Z. D. ET AL., ZHONGHUA WEI CHANG WAI KE.ZA ZHI., vol. 10, 2007, pages 365 - 367
GUALCO, G. ET AL., APPL.IMMUNOHISTOCHEM.MOL.MORPHOL., vol. 18, 2010, pages 301 - 310
GUERRERO, K. ET AL., GYNECOL.ONCOL, vol. 125, 2012, pages 720 - 726
GUO, J. T. ET AL., ZHONGHUA ZHONG.LIU ZA ZHI., vol. 31, 2009, pages 528 - 531
GUPTA, A. K. ET AL., MED J ARMED.FORCES.LNDIA, vol. 72, 2016, pages S37 - S42
GUSTAFSSON, C. ET AL., TRENDS BIOTECHNOL., vol. 22, 2004, pages 346 - 353
HAASS, N. K. ET AL., PIGMENT CELL RES, vol. 18, 2005, pages 150 - 159
HAEBERLE, H. ET AL., NEOPLASIA, vol. 14, 2012, pages 666 - 669
HALL, R. D. ET AL., CANCER CONTROL, vol. 20, 2013, pages 22 - 31
HAMILTON, K. E. ET AL., MOL.CANCER RES, vol. 13, 2015, pages 1478 - 1486
HAN, J. ET AL., WORLD J SURG.ONCOL, vol. 10, 2012, pages 37
HAN, Y. D. ET AL., ONCOTARGET, vol. 8, 2017, pages 1871 - 1883
HAN, Y. ET AL., EUR.J CELL BIOL, vol. 94, 2015, pages 642 - 652
HANAFUSA, H. ET AL., SEIKAGAKU, vol. 83, 2011, pages 1127 - 1131
HARNDAHL, M. ET AL., EUR.J IMMUNOL., vol. 42, 2012, pages 1405 - 1416
HASE, H. ET AL., MOL.CANCER RES, vol. 12, 2014, pages 1807 - 1817
HASEGAWA, H. ET AL., ARCH.PATHOL.LAB MED., vol. 122, 1998, pages 551 - 554
HASHEM, N. N. ET AL., INT.J BIOL MARKERS, vol. 25, 2010, pages 32 - 37
HASHIMOTO, Y. ET AL., ONCOTARGET, 2017
HAYASHI, S. I. ET AL., ENDOCR.RELAT CANCER, vol. 10, 2003, pages 193 - 202
HAYASHIDA, T. ET AL., PROC.NATL.ACAD.SCI.U.S.A, vol. 107, 2010, pages 1100 - 1105
HEEG, S. ET AL., GASTROENTEROLOGY, vol. 151, 2016, pages 540 - 553
HEERMA VAN VOSS, M. R. ET AL., HISTOPATHOLOGY, vol. 65, 2014, pages 814 - 827
HEMMINGER, J. A. ET AL., MOD.PATHOL., vol. 27, 2014, pages 1238 - 1245
HENNARD, C. ET AL., J PATHOL., vol. 209, 2006, pages 430 - 435
HEUBACH, J. ET AL., MOL.CANCER, vol. 14, 2015, pages 108
HIGGINS, J. ET AL., HORM.CANCER, vol. 6, 2015, pages 67 - 86
HILDEBRANDT, M. O. ET AL., BONE MARROW TRANSPLANT., vol. 22, 1998, pages 771 - 775
HIRAMOTO, T. ET AL., ONCOGENE, vol. 18, 1999, pages 3422 - 3426
HIRATA, T. ET AL., ONCOL REP., vol. 33, 2015, pages 2052 - 2060
HIROUMI, H. ET AL., INT.J CANCER, vol. 93, 2001, pages 786 - 791
HOFF, P. M. ET AL., SURG.ONCOL CLIN N.AM., vol. 26, 2017, pages 57 - 71
HOFFMANN, N. E. ET AL., CANCER, vol. 112, 2008, pages 1471 - 1479
HOFMANN, M. C. ET AL., EUR.UROL., vol. 23, 1993, pages 38 - 44
HOLM, C. ET AL., LEUK.RES, vol. 30, 2006, pages 254 - 261
HONRADO, E. ET AL., CRIT REV ONCOL HEMATOL., vol. 59, 2006, pages 27 - 39
HORIUCHI, S. ET AL., J PATHOL., vol. 200, 2003, pages 568 - 576
HORVATH, A. ET AL., WORLD J GASTROENTEROL., vol. 10, 2004, pages 152 - 154
HOSHINO, Y. ET AL., MOL.CANCER, vol. 13, 2014, pages 102
HOU, Z. ET AL., MOL.CANCER THER., 2017
HU, S. ET AL., J CANCER RES CLIN ONCOL, vol. 140, 2014, pages 883 - 893
HU, X. T. ET AL., CELL PROLIF., vol. 47, 2014, pages 200 - 210
HUANG, K. ET AL., CHIN J CANCER RES, vol. 26, 2014, pages 72 - 80
HUANG, X. ET AL., CELL PROLIF., vol. 48, 2015, pages 593 - 599
HUDOLIN, T. ET AL., J TRANSL.MED, vol. 11, 2013, pages 123
HUR, H. ET AL., J CANCER, vol. 7, 2016, pages 768 - 773
HUSSEIN, Y. M. ET AL., MED.ONCOL, vol. 29, 2012, pages 3055 - 3062
HWANG, M. L. ET AL., J IMMUNOL., vol. 179, 2007, pages 5829 - 5838
IDBAIH, A., REV NEUROL.(PARIS, vol. 167, 2011, pages 691 - 698
INGARAMO, P. I. ET AL., MOL.CELL ENDOCRINOL., vol. 425, 2016, pages 37 - 47
ISHIDA, S. ET AL., BIOCHEM.BIOPHYS.RES COMMUN., vol. 339, 2006, pages 325 - 330
ISHIKAWA, K. ET AL., MOL.BIOL CELL, vol. 23, 2012, pages 1294 - 1306
ISHIKAWA, S. ET AL., CELL TISSUE RES, vol. 337, 2009, pages 381 - 391
ITESAKO, T. ET AL., PLOS.ONE, vol. 9, 2014, pages e84311
IU, X. ET AL., INT.LMMUNOPHARMACOL., vol. 25, 2015, pages 416 - 424
JACOBS, J. ET AL., ONCOTARGET, vol. 6, 2015, pages 13462 - 13475
JACOBS, J. ET AL., PHARMACOL.THER., vol. 155, 2015, pages 1 - 10
JAMES, S. R. ET AL., EPIGENETICS., vol. 8, 2013, pages 849 - 863
JANG, B. G. ET AL., VIRCHOWS ARCH., vol. 467, 2015, pages 393 - 403
JENG, Y. M. ET AL., BR.J SURG., vol. 96, 2009, pages 66 - 73
JI, P. ET AL., ONCOGENE, vol. 24, 2005, pages 2739 - 2744
JIANG, D. ET AL., PLOS.ONE, vol. 9, 2014, pages e96822
JIANG, Y. ET AL., MOL.ONCOL, vol. 10, 2016, pages 292 - 302
JIANG, Y. ET AL., ONCOTARGET., vol. 6, 2015, pages 39865 - 39876
JIAO, T. T. ET AL., INT.J CLIN EXP.PATHOL., vol. 6, 2013, pages 3036 - 3041
JIN, H. ET AL., TUMOUR.BIOL, vol. 27, 2006, pages 274 - 282
JNAWALI, H. N. ET AL., J NAT PROD., vol. 77, 2014, pages 258 - 263
JOHN, T. ET AL., CLIN CANCER RES, vol. 14, 2008, pages 3291 - 3298
JUNG, D. B. ET AL., ONCOTARGET, vol. 6, 2015, pages 4992 - 5004
JUNG, G. ET AL., PROC NATL ACAD SCI U S A, vol. 84, 1987, pages 4611 - 4615
KALEJS, M. ET AL., BMC.CANCER, vol. 6, 2006, pages 6
KANNAN, K. ET AL., PROC.NATL.ACAD.SCI.U.S.A, vol. 112, 2015, pages E1272 - E1277
KARLGREN, M. ET AL., EXPERT.OPIN.THER.TARGETS., vol. 11, 2007, pages 61 - 67
KARPF, A. R. ET AL., MOL.CANCER RES, vol. 7, 2009, pages 523 - 535
KASASHIMA, H. ET AL., CANCER LETT., vol. 354, 2014, pages 438 - 446
KAUFMAN, L. ET AL., J AM.SOC.NEPHROL., vol. 15, 2004, pages 1721 - 1730
KAZI, J. A. ET AL., NEUROPEPTIDES, vol. 41, 2007, pages 227 - 231
KEDAGE, V. ET AL., CELL REP., vol. 17, 2016, pages 1289 - 1301
KELD, R. ET AL., BR.J CANCER, vol. 105, 2011, pages 124 - 130
KELD, R. ET AL., MOL.CANCER, vol. 9, 2010, pages 313
KELEMEN, L. E. ET AL., NAT GENET., vol. 47, 2015, pages 888 - 897
KELLY, Z. ET AL., INT.J CANCER, vol. 139, 2016, pages 1608 - 1617
KERNS, S. L. ET AL., J UROL., vol. 190, 2013, pages 102 - 108
KEVANS, D. ET AL., INT J SURG.PATHOL., vol. 19, 2011, pages 751 - 760
KHAN, F. S. ET AL., HEPATOL.INT., vol. 11, 2017, pages 45 - 53
KHAN, M. F. ET AL., TRANSL.ONCOL, vol. 5, 2012, pages 85 - 91
KIBBE, A. H.: "Handbook of Pharmaceutical Excipients", 2000
KIKKAWA, Y. ET AL., EXP.CELL RES, vol. 314, 2008, pages 2579 - 2590
KIKKAWA, Y. ET AL., EXP.CELL RES, vol. 328, 2014, pages 197 - 206
KIKKAWA, Y. ET AL., J BIOL CHEM, vol. 288, 2013, pages 30990 - 31001
KIM, B. K. ET AL., J DERMATOL.SCI., vol. 79, 2015, pages 137 - 147
KIM, B. R. ET AL., CELL SIGNAL., vol. 26, 2014, pages 1765 - 1773
KIM, T. D. ET AL., J CLIN INVEST, vol. 126, 2016, pages 706 - 720
KIM, T. H. ET AL., J KOREAN MED SCI., vol. 30, 2015, pages 155 - 161
KIM, Y. D. ET AL., INT.J MOL.MED., vol. 29, 2012, pages 656 - 662
KIM, Y. H. ET AL., ANN.SURG.ONCOL, vol. 18, 2011, pages 2338 - 2347
KING, M. L. ET AL., ONCOGENE, vol. 34, 2015, pages 3452 - 3462
KINOSHITA, T. ET AL., INT.LMMUNOL., vol. 18, 2006, pages 1701 - 1706
KINOSHITA, T. ET AL., J BIOL CHEM, vol. 280, 2005, pages 21720 - 21725
KIRKOVA, M. ET AL., PHARMACOL.REP., vol. 61, 2009, pages 1163 - 1172
KLATKA, J. ET AL., EUR.ARCH.OTORHINOLARYNGOL., vol. 270, 2013, pages 2683 - 2693
KLAUKE, K. ET AL., NAT CELL BIOL, vol. 15, 2013, pages 353 - 362
KLEEFF, J. ET AL., NAT REV DIS.PRIMERS., vol. 2, 2016, pages 16022
KNUDSEN, K. A. ET AL., J CELL BIOCHEM., vol. 95, 2005, pages 488 - 496
KO, A. ET AL., BMB.REP., vol. 49, 2016, pages 598 - 606
KOCAK, H. ET AL., CELL DEATH.DIS., vol. 4, 2013
KOHRT, D. ET AL., CELL CYCLE, vol. 13, 2014, pages 62 - 71
KONTOS, C. K. ET AL., CLIN CHEM LAB MED, vol. 54, 2016, pages 315 - 324
KOONRUNGSESOMBOON, N. ET AL., CANCER EPIDEMIOL., vol. 39, 2015, pages 487 - 496
KORR, D. ET AL., CELL SIGNAL., vol. 18, 2006, pages 910 - 920
KOUNTOURAKIS, P. ET AL., THROMB.HAEMOST., vol. 101, 2009, pages 541 - 546
KREPISCHI, A. C. ET AL., MOL.CYTOGENET., vol. 9, 2016, pages 20
KRIEG, A. M., NAT REV.DRUG DISCOV., vol. 5, 2006, pages 471 - 484
KRUHLAK, M. ET AL., NATURE, vol. 447, 2007, pages 730 - 734
KUBALL, J. ET AL., BLOOD, vol. 109, 2007, pages 2331 - 2338
KUGA, T. ET AL., J CELL SCI., vol. 126, 2013, pages 4721 - 4731
KUGA, T. ET AL., SCI.REP., vol. 6, 2016, pages 26557
KUMARI, A. ET AL., BMC.RES NOTES, vol. 9, 2016, pages 92
KUMAR-SINHA, C. ET AL., GENOME MED, vol. 7, 2015, pages 129
KUNER, R. ET AL., J MOL.MED (BERL, vol. 91, 2013, pages 237 - 248
KUO, C. T. ET AL., CANCER LETT., vol. 378, 2016, pages 104 - 110
KUPPERS, R. ET AL., J CLIN INVEST, vol. 111, 2003, pages 529 - 537
KURSCHEID, S. ET AL., GENOME BIOL, vol. 16, 2015
KWON, O. S. ET AL., ONCOTARGET, vol. 6, 2015, pages 41916 - 41928
LA, VECCHIA C., EUR.J CANCER PREV., vol. 10, 2001, pages 125 - 129
LACOBUZIO-DONAHUE, C. A. ET AL., CANCER RES, vol. 63, 2003, pages 8614 - 8622
LALLY, K. M. ET AL., INT.J CANCER, vol. 93, 2001, pages 841 - 847
LAPIN, V. ET AL., ONCOGENESIS, vol. 3, 2014, pages e133
LATINI, F. R. ET AL., BLOOD CELLS MOL.DIS., vol. 50, 2013, pages 161 - 165
LAWRENSON, K. ET AL., INT.J CANCER, vol. 136, 2015, pages 1390 - 1401
LAWRENSON, K. ET AL., NAT COMMUN., vol. 6, 2015, pages 8234
LAZARO-IBANEZ, E. ET AL., BMC.CANCER, vol. 17, 2017, pages 92
LEDERER, M. ET AL., SEMIN.CANCER BIOL, vol. 29, 2014, pages 3 - 12
LEE, E. ET AL., BMB.REP., vol. 46, 2013, pages 594 - 599
LEE, O. H. ET AL., MOL.CELL PROTEOMICS., vol. 10, 2011, pages M110
LEONG, S. R. ET AL., MOL.PHARM., vol. 12, 2015, pages 1717 - 1729
LEUNG, F. ET AL., CANCER EPIDEMIOL.BIOMARKERS PREV., vol. 25, 2016, pages 1333 - 1340
LI, B. ET AL., CELL BIOCHEM.BIOPHYS., vol. 70, 2014, pages 1363 - 1368
LI, B. ET AL., ONCOTARGET, 2016
LI, H. ET AL., GYNECOL.ONCOL, vol. 84, 2002, pages 216 - 221
LI, L. ET AL., CYTOKINE, vol. 89, 2017, pages 173 - 178
LI, L. ET AL., ZHONGGUO SHI YAN.XUE.YE.XUE.ZA ZHI., vol. 24, 2016, pages 326 - 331
LI, M. ET AL., CLIN CANCER RES, vol. 11, 2005, pages 1809 - 1814
LI, M. ET AL., ONCOTARGET, vol. 7, 2016, pages 51503 - 51514
LI, Q. ET AL., J GASTROENTEROL.HEPATOL., vol. 29, 2014, pages 835 - 842
LI, W. M. ET AL., J SURG.ONCOL, 2016
LI, Z. ET AL., CANCER RES, vol. 76, 2016, pages 619 - 629
LIANG, X. ET AL., ONCOTARGET, vol. 7, 2016, pages 52207 - 52217
LIDDY, N. ET AL., NAT MED., vol. 18, 2012, pages 980 - 987
LILJA-MAULA, L. ET AL., J COMP PATHOL., vol. 150, 2014, pages 399 - 407
LIM, J. Y. ET AL., WORLD J GASTROENTEROL., vol. 19, 2013, pages 7078 - 7088
LIN, J. ET AL., CLIN CANCER RES, vol. 10, 2004, pages 5708 - 5716
LIN, L. ET AL., ONCOL LETT., vol. 6, 2013, pages 740 - 744
LIN, Q. ET AL., J CANCER RES CLIN ONCOL, vol. 135, 2009, pages 1675 - 1684
LIN, Z. ET AL., DIAGN.PATHOL., vol. 8, 2013, pages 133
LINN, D. E. ET AL., PLOS.ONE, vol. 10, 2015, pages e0120628
LINZ, K. ET AL., J PHARMACOL.EXP.THER., vol. 349, 2014, pages 535 - 548
LIU, D. B. ET AL., WORLD J GASTROENTEROL., vol. 11, 2005, pages 1562 - 1566
LIU, M. ET AL., CELL MOL.NEUROBIOL., vol. 34, 2014, pages 913 - 923
LIU, Q. ET AL., J BIOL CHEM, vol. 286, 2011, pages 29951 - 29963
LIU, R. ET AL., CANCER BIOL THER., vol. 16, 2015, pages 317 - 324
LIU, W. ET AL., MOL.CLIN ONCOL, vol. 2, 2014, pages 219 - 225
LIU, X. ET AL., BIOMED.PHARMACOTHER., vol. 88, 2017, pages 595 - 602
LIU, Y. ET AL., INT.J GYNECOL.CANCER, vol. 23, 2013, pages 304 - 311
LJUNGGREN, H. G. ET AL., J EXP.MED., vol. 162, 1985, pages 1745 - 1759
LLAURADO, M. ET AL., INT.J CANCER, vol. 130, 2012, pages 1532 - 1543
LLAURADO, M. ET AL., MOL.CANCER RES, vol. 10, 2012, pages 914 - 924
LOANNIDIS, P. ET AL., ANTICANCER RES, vol. 23, 2003, pages 2179 - 2183
LONGENECKER, B. M. ET AL., ANN N.Y.ACAD.SCI., vol. 690, 1993, pages 276 - 291
LOPEZ, R. ET AL., INT.J GYNECOL.CANCER, vol. 16, 2006, pages 1289 - 1296
LOPEZ-ROMERO, R. ET AL., REV MED INST.MEX.SEGURO.SOC., vol. 53, no. 2, 2015, pages S188 - S193
LORINCZ, A. T., ACTA CYTOL., vol. 60, 2016, pages 501 - 512
LOSE, F. ET AL., BIOL CHEM, vol. 393, 2012, pages 403 - 412
LOW, G. M. ET AL., ORAL ONCOL, vol. 61, 2016, pages 27 - 30
LUKAS, T. ET AL., PROC.NATL.ACAD.SCI.U.S.A, vol. 78, 1981, pages 2791 - 2795
LUNARDI, A. ET AL., CANCER DISCOV, vol. 5, 2015, pages 550 - 563
LUNDBLAD, R. L., CHEMICAL REAGENTS FOR PROTEIN MODIFICATION 3RD, 2004
LUO, H. ET AL., INT.J CLIN EXP.MED, vol. 7, 2014, pages 1244 - 1254
LUO, P. ET AL., ONCOL REP., 2017
LUOSTARI, K. ET AL., PLOS.ONE, vol. 9, 2014, pages e102519
LV, G. Q. ET AL., BIOCHEM.CELL BIOL, vol. 92, 2014, pages 379 - 389
LV, L. ET AL., CANCER LETT., vol. 357, 2015, pages 105 - 113
LV, X. ET AL., J EXP.CLIN CANCER RES, vol. 34, 2015, pages 133
MA, K. ET AL., CLIN EPIGENETICS, vol. 8, 2016, pages 43
MA, Y. ET AL., BIOSENS.BIOELECTRON., vol. 85, 2016, pages 641 - 648
MA, Z. ET AL., INT.J CLIN EXP.PATHOL., vol. 8, 2015, pages 5071 - 5079
MACLEAN, J. A. ET AL., PLOS.ONE, vol. 11, 2016, pages e0156109
MAHAJAN, A., HUM.PATHOL., vol. 51, 2016, pages 64 - 74
MAINE, E. A. ET AL., ONCOTARGET, vol. 7, 2016, pages 14708 - 14726
MAINES-BANDIERA, S. ET AL., INT.J GYNECOL.CANCER, vol. 20, 2010, pages 16 - 22
MAMANE, Y. ET AL., J INTERFERON CYTOKINE RES, vol. 22, 2002, pages 135 - 143
MANTIA-SMALDONE, G. M. ET AL., HUM.VACCIN.LMMUNOTHER., vol. 8, 2012, pages 1179 - 1191
MANZELLA, L. ET AL., CURR.CANCER DRUG TARGETS., vol. 16, 2016, pages 594 - 605
MAO, L. ET AL., CANCER RES, vol. 71, 2011, pages 4314 - 4324
MARCINKIEWICZ, K. M. ET AL., EXP.CELL RES, vol. 320, 2014, pages 128 - 143
MARCINKIEWICZ, K. M. ET AL., J CELL PHYSIOL, vol. 229, 2014, pages 1405 - 1416
MARLOW, L. A. ET AL., J CELL SCI., vol. 125, 2012, pages 4253 - 4263
MARUTA, S. ET AL., APMIS, vol. 117, 2009, pages 791 - 796
MARZESE, D. M. ET AL., HUM.MOL.GENET., vol. 23, 2014, pages 226 - 238
MASAMOTO, I. ET AL., LEUK.LYMPHOMA, vol. 57, 2016, pages 685 - 691
MASON, J. M. ET AL., NUCLEIC ACIDS RES., vol. 43, 2015, pages 3180 - 3196
MAWRIN, C. ET AL., J NEUROONCOL., vol. 99, 2010, pages 379 - 391
MCCORMACK, E. ET AL., CANCER IMMUNOL.IMMUNOTHER., vol. 62, 2013, pages 773 - 785
MEDINA-AGUILAR, R. ET AL., DATA BRIEF., vol. 11, 2017, pages 169 - 182
MEHTA, A. ET AL., BREAST, vol. 23, 2014, pages 2 - 9
MELIN, B., CURR.OPIN.ONCOL, vol. 23, 2011, pages 643 - 647
MENEZES, J. ET AL., LEUKEMIA, vol. 28, 2014, pages 823 - 829
MERCER, K. E. ET AL., ADV.EXP.MED BIOL, vol. 815, 2015, pages 185 - 195
MERCER, K. E. ET AL., CANCER PREV.RES (PHILA, vol. 7, 2014, pages 675 - 685
MESQUITA, D. ET AL., ONCOTARGET, vol. 6, 2015, pages 5217 - 5236
MEZIERE, C. ET AL., J IMMUNOL, vol. 159, 1997, pages 3230 - 3237
MICHAELIDOU, K. ET AL., BREAST CANCER RES TREAT., vol. 152, 2015, pages 323 - 336
MILLAN, J. L. ET AL., CRIT REV CLIN LAB SCI., vol. 32, 1995, pages 1 - 39
MITSUHASHI, K. ET AL., INT.J HEMATOL., vol. 100, 2014, pages 88 - 95
MIYAZAKI, M. ET AL., IMMUNITY, vol. 28, 2008, pages 231 - 245
MIYOSHI, Y. ET AL., MED.MOL.MORPHOL., vol. 43, 2010, pages 193 - 196
MIZUNO, K. ET AL., INT.J ONCOL, vol. 48, 2016, pages 450 - 460
MOON, H. J. ET AL., BIOORG.CHEM, vol. 57, 2014, pages 231 - 241
MOORE, K. N. ET AL., J CLIN ONCOL, 2016
MORGAN, R. A. ET AL., SCIENCE, vol. 314, 2006, pages 126 - 129
MOROY, T. ET AL., SEMIN.LMMUNOL., vol. 23, 2011, pages 379 - 387
MORTARA, L. ET AL., CLIN CANCER RES., vol. 12, 2006, pages 3435 - 3443
MOSKVINA, L. V. ET AL., ARKH.PATOL., vol. 72, 2010, pages 58 - 61
MOUSSA, O. ET AL., J CELL BIOCHEM., vol. 108, 2009, pages 1389 - 1398
MUMBERG, D. ET AL., PROC.NATL.ACAD.SCI.U.S.A, vol. 96, 1999, pages 8633 - 8638
NABESHIMA, K. ET AL., DIAGN.CYTOPATHOL., vol. 44, 2016, pages 774 - 780
NALLA, A. K. ET AL., MOL.CARCINOG, vol. 55, 2016, pages 1761 - 1771
NAWAZ, I. ET AL., ONCOTARGET, vol. 6, 2015, pages 31493 - 31507
NISHIDA, C. R. ET AL., MOL.PHARMACOL., vol. 78, 2010, pages 497 - 502
NISKAKOSKI, A. ET AL., EPIGENETICS, vol. 9, 2014, pages 1577 - 1587
NOAH, T. K. ET AL., GASTROENTEROLOGY, vol. 144, 2013, pages 1012 - 1023
NOTARIDOU, M. ET AL., INT.J CANCER, vol. 128, 2011, pages 2063 - 2074
NOTARO, S. ET AL., BMC.CANCER, vol. 16, 2016, pages 589
NOUBISSI, F. K. ET AL., J INVEST DERMATOL., vol. 134, 2014, pages 1718 - 1724
OBIEZU, C. V. ET AL., CANCER LETT., vol. 224, 2005, pages 1 - 22
OH, S. ET AL., BIOCHIM.BIOPHYS.ACTA, vol. 1826, 2012, pages 1 - 12
OHNO, S. ET AL., ANTICANCER RES, vol. 28, 2008, pages 2493 - 2497
OKADA, K. ET AL., CANCER SCI., vol. 95, 2004, pages 949 - 954
OKAMOTO, O. K. ET AL., BIOCHIM.BIOPHYS.ACTA, vol. 1769, 2007, pages 437 - 442
OLIVEIRA-COSTA, J. P. ET AL., ONCOTARGET, vol. 6, 2015, pages 20902 - 20920
ORSINI, G. ET AL., PATHOL.ONCOL RES, vol. 20, 2014, pages 267 - 276
ORWAT, D. E. ET AL., ARCH.PATHOL.LAB MED, vol. 136, 2012, pages 333 - 338
OSTERGAARD, PEDERSEN L. ET AL., EUR.J IMMUNOL., vol. 31, 2001, pages 2986 - 2996
OTTAVIANI, S. ET AL., CANCER IMMUNOL.IMMUNOTHER., vol. 55, 2006, pages 867 - 872
OTTE, M. ET AL., CANCER RES, vol. 61, 2001, pages 6682 - 6687
OUE, N. ET AL., CANCER SCI., vol. 106, 2015, pages 951 - 958
PACHOLCZYK, M. ET AL., MED PR, vol. 67, 2016, pages 255 - 266
PAGNOTTA, S. M. ET AL., PLOS.ONE, vol. 8, 2013, pages e72638
PAI, V. P. ET AL., BREAST CANCER RES, vol. 11, 2009, pages R81
PAL, M. ET AL., J BIOL CHEM, vol. 288, 2013, pages 12222 - 12231
PALACIOS, J. ET AL., PATHOBIOLOGY, vol. 75, 2008, pages 85 - 94
PALIOURAS, M. ET AL., BREAST CANCER RES TREAT., vol. 102, 2007, pages 7 - 18
PALIOURAS, M. ET AL., MOL.ONCOL, 2008, pages 413 - 424
PALIOURAS, M. ET AL., TUMOUR.BIOL, vol. 29, 2008, pages 63 - 75
PALMA, M. ET AL., BMC.CLIN PATHOL., vol. 12, 2012, pages 2
PAPACHRISTOPOULOU, G. ET AL., TUMOUR.BIOL, vol. 34, 2013, pages 369 - 378
PAPADAKIS, A. I. ET AL., CELL RES, vol. 25, 2015, pages 445 - 458
PAPADOPOULOU-BOUTIS, A. ET AL., CANCER DETECT.PREV., vol. 8, 1985, pages 141 - 150
PAREDES, J. ET AL., BIOCHIM.BIOPHYS.ACTA, vol. 1826, 2012, pages 297 - 311
PAREDES, J. ET AL., BREAST CANCER RES, vol. 9, 2007, pages 214
PARRIS, T. Z. ET AL., BMC.CANCER, vol. 14, 2014, pages 324
PARRIS, T. Z. ET AL., CLIN CANCER RES, vol. 16, 2010, pages 3860 - 3874
PATHIRAJA, T. N. ET AL., SCI.TRANSL.MED, vol. 6, 2014, pages 229ra41
PATRICK, A. N. ET AL., NAT STRUCT.MOL.BIOL, vol. 20, 2013, pages 447 - 453
PATTANI, K. M. ET AL., PLOS.ONE, vol. 7, 2012, pages e45534
PAULINA BALBAS; ARGELIA LORENCE: "Methods in Molecular Biology Recombinant Gene Expression, Reviews and Protocols"
PEETERS, M. C. ET AL., CELL SIGNAL., vol. 27, 2015, pages 2579 - 2588
PELKONEN, M. ET AL., BMC.CANCER, vol. 15, 2015, pages 431
PENG, H. X. ET AL., BIOMED.RES INT., vol. 2015, 2015
PEREIRA, B. ET AL., NUCLEIC ACIDS RES, vol. 41, 2013, pages 3986 - 3999
PEREZ, C. A. ET AL., EXPERT.REV ANTICANCER THER., vol. 11, 2011, pages 1599 - 1605
PETERSEN, G. M., SEMIN.ONCOL, vol. 43, 2016, pages 548 - 553
PETRAU, C. ET AL., J CANCER, vol. 5, 2014, pages 761 - 764
PICH, C. ET AL., BR.J CANCER, vol. 114, 2016, pages 63 - 70
PICH, C. ET AL., PLOS.ONE, vol. 11, 2016, pages e0148095
PICKARD, M. R. ET AL., BREAST CANCER RES, vol. 11, 2009, pages R60
PINEDA, C. T. ET AL., CELL, vol. 160, 2015, pages 715 - 728
PIURA, B. ET AL., HAREFUAH, vol. 144, 2005, pages 261 - 5,303,302
PLANAGUMA, J. ET AL., HUM.PATHOL., vol. 42, 2011, pages 57 - 67
PLANQUE, C. ET AL., BIOL CHEM, vol. 389, 2008, pages 781 - 786
PLANQUE, C. ET AL., CLIN CANCER RES, vol. 14, 2008, pages 1355 - 1362
PLANQUE, C. ET AL., CLIN CHEM, vol. 56, 2010, pages 987 - 997
PLEBANSKI, M. ET AL., EUR.J IMMUNOL, vol. 25, 1995, pages 1783 - 1787
POLLACK, S. M. ET AL., PLOS.ONE, vol. 7, 2012, pages e32165
POLLARD, C. ET AL., EXPERT.REV MOL.MED, vol. 12, 2010, pages e10
PONTE, J. F. ET AL., NEOPLASIA, vol. 18, 2016, pages 775 - 784
PONZONI, M. ET AL., ANN.ONCOL, vol. 25, 2014, pages 316 - 322
POPOV, N. ET AL., EPIGENETICS, vol. 5, 2010, pages 685 - 690
PORTA, C. ET AL., VIROLOGY, vol. 202, 1994, pages 949 - 955
POWER, P. F. ET AL., J ORTHOP.RES, vol. 31, 2013, pages 493 - 501
PRASAD, M. L. ET AL., HEAD NECK, vol. 26, 2004, pages 1053 - 1057
PU, X. ET AL., CLIN PHARMACOL.THER., vol. 96, 2014, pages 609 - 615
PYLE-CHENAULT, R. A. ET AL., TUMOUR.BIOL, vol. 26, 2005, pages 245 - 257
QIN, Y. ET AL., CHIN MED.J (ENGL., vol. 127, 2014, pages 1666 - 1671
R. LUNDBLAD: "Chemical Reagents for Protein Modification", 2004, CRC PRESS
RABIEN, A. ET AL., TUMOUR.BIOL, vol. 29, 2008, pages 1 - 8
RAEISOSSADATI, R. ET AL., TUMOUR.BIOL, vol. 35, 2014, pages 5299 - 5305
RAHMATPANAH, F. B. ET AL., LEUKEMIA, vol. 20, 2006, pages 1855 - 1862
RAJAPAKSE, S. ET AL., ZOOLOG.SCI., vol. 24, 2007, pages 774 - 780
RAMMENSEE, H. ET AL., IMMUNOGENETICS, vol. 50, 1999, pages 213 - 219
RAMOS-SOLANO, M. ET AL., EXP.CELL RES, vol. 335, 2015, pages 39 - 50
RAPOPORT, A. P. ET AL., NAT MED, vol. 21, 2015, pages 914 - 921
RASMUSSEN, S. L. ET AL., COLORECTAL DIS., vol. 18, 2016, pages 549 - 561
RASTELLI, F. ET AL., TUMORI, vol. 96, 2010, pages 875 - 888
RAUSCHER, G. H. ET AL., BMC.CANCER, vol. 15, 2015, pages 816
RAVENNI, N. ET AL., MABS., vol. 6, 2014, pages 86 - 94
RECK, M., ANN.ONCOL, vol. 23, no. 8, 2012, pages viii28 - viii34
RESENDE, C. ET AL., HELICOBACTER, vol. 16, no. 1, 2011, pages 38 - 44
REYES, C. ET AL., APPL.IMMUNOHISTOCHEM.MOL.MORPHOL., vol. 21, 2013, pages 283 - 286
REYNIERS, L. ET AL., J NEUROCHEM., vol. 131, 2014, pages 239 - 250
RIBEIRO, A. S. ET AL., FRONT ONCOL, vol. 4, 2014, pages 371
RICKETTS, C. J. ET AL., PLOS.ONE, vol. 9, 2014, pages e85621
RIEDEL, S. S. ET AL., J CLIN INVEST, vol. 126, 2016, pages 1438 - 1450

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11213578B2 (en) 2017-03-03 2022-01-04 Treos Bio Limited Vaccine
US11426452B2 (en) 2017-03-03 2022-08-30 Treos Bio Limited Vaccine
US11628211B2 (en) 2017-03-03 2023-04-18 Treos Bio Limited Vaccine
WO2020048990A1 (fr) * 2018-09-04 2020-03-12 Treos Bio Zrt Vaccins peptidiques
CN113329761A (zh) * 2018-09-04 2021-08-31 特雷斯生物有限公司 肽疫苗
JP2021536487A (ja) * 2018-09-04 2021-12-27 トレオス バイオ リミテッド ペプチドワクチン
US11666644B2 (en) 2018-09-04 2023-06-06 Treos Bio Limited Peptide vaccines
WO2020127546A3 (fr) * 2018-12-18 2020-09-17 Immatics Biotechnologies Gmbh Immunothérapie à l'aide de peptides restreints par b*08 et combinaison de peptides contre des cancers et méthodes associées
EP3990483A4 (fr) * 2019-06-25 2024-02-21 Université de Montréal Nouveaux antigènes spécifiques à une tumeur pour le cancer de l'ovaire
CN113967261A (zh) * 2020-07-24 2022-01-25 中国科学院大连化学物理研究所 Folr1抑制剂的应用和治疗肝癌药物混合物
CN113967261B (zh) * 2020-07-24 2023-02-03 中国科学院大连化学物理研究所 Folr1抑制剂的应用和治疗肝癌药物混合物
WO2022225057A1 (fr) * 2021-04-23 2022-10-27 Vlp Therapeutics, Inc. Immunothérapie ciblant la galectine

Also Published As

Publication number Publication date
TW201831507A (zh) 2018-09-01
MA47367A (fr) 2019-12-04
MA47367B1 (fr) 2023-06-28
TWI796314B (zh) 2023-03-21

Similar Documents

Publication Publication Date Title
US11919940B2 (en) Peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
TWI796314B (zh) 用於卵巢癌和其他癌症免疫治療的新型肽和肽組合物
US11840562B2 (en) Peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
NZ789493A (en) Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
NZ796665A (en) Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18702642

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2018212584

Country of ref document: AU

Date of ref document: 20180126

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 3048108

Country of ref document: CA

ENP Entry into the national phase

Ref document number: 2019539937

Country of ref document: JP

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 20197022277

Country of ref document: KR

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112019015237

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 2018702642

Country of ref document: EP

Effective date: 20190827

ENP Entry into the national phase

Ref document number: 112019015237

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20190724