WO2008032153A3 - Calreticulin for its use as a medication for the treatment of cancer in a mammal - Google Patents
Calreticulin for its use as a medication for the treatment of cancer in a mammal Download PDFInfo
- Publication number
- WO2008032153A3 WO2008032153A3 PCT/IB2007/002502 IB2007002502W WO2008032153A3 WO 2008032153 A3 WO2008032153 A3 WO 2008032153A3 IB 2007002502 W IB2007002502 W IB 2007002502W WO 2008032153 A3 WO2008032153 A3 WO 2008032153A3
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- erp57
- crt
- calreticulin
- anthracyclines
- translocation
- Prior art date
Links
- 102000004082 Calreticulin Human genes 0.000 title abstract 11
- 108090000549 Calreticulin Proteins 0.000 title abstract 11
- 241000124008 Mammalia Species 0.000 title abstract 2
- 206010028980 Neoplasm Diseases 0.000 title 1
- 201000011510 cancer Diseases 0.000 title 1
- 229940079593 drug Drugs 0.000 title 1
- 239000003814 drug Substances 0.000 title 1
- 101150039088 PDIA3 gene Proteins 0.000 abstract 8
- 102100037097 Protein disulfide-isomerase A3 Human genes 0.000 abstract 8
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 abstract 4
- 229940045799 anthracyclines and related substance Drugs 0.000 abstract 4
- 230000005945 translocation Effects 0.000 abstract 4
- 101000611643 Homo sapiens Protein phosphatase 1 regulatory subunit 15A Proteins 0.000 abstract 2
- 108010059000 Protein Phosphatase 1 Proteins 0.000 abstract 2
- 102000005569 Protein Phosphatase 1 Human genes 0.000 abstract 2
- 102100040714 Protein phosphatase 1 regulatory subunit 15A Human genes 0.000 abstract 2
- 230000001093 anti-cancer Effects 0.000 abstract 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 abstract 2
- 229960005420 etoposide Drugs 0.000 abstract 2
- 230000028993 immune response Effects 0.000 abstract 2
- 230000002163 immunogen Effects 0.000 abstract 2
- 230000005847 immunogenicity Effects 0.000 abstract 2
- 229960004857 mitomycin Drugs 0.000 abstract 2
- 210000004881 tumor cell Anatomy 0.000 abstract 2
- 241000699670 Mus sp. Species 0.000 abstract 1
- 206010057249 Phagocytosis Diseases 0.000 abstract 1
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 230000001640 apoptogenic effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 abstract 1
- 230000030833 cell death Effects 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000002512 chemotherapy Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 210000004443 dendritic cell Anatomy 0.000 abstract 1
- 238000001514 detection method Methods 0.000 abstract 1
- 230000004927 fusion Effects 0.000 abstract 1
- 238000003197 gene knockdown Methods 0.000 abstract 1
- 230000037449 immunogenic cell death Effects 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 239000000411 inducer Substances 0.000 abstract 1
- 230000036512 infertility Effects 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 abstract 1
- 230000008782 phagocytosis Effects 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/45—Transferases (2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Reproductive Health (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Transplantation (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Biochemistry (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Anthracyclines-treated tumor cells are particularly effective in eliciting an anti-cancer immune response, where the rDNA-damaging agents, such as etoposide and mitomycin C do not induce immunogenic cell death. Anthracyclines induce the rapid, pre-apoptotic translocation of calreticulin (CRT) and/or ERP57 to the cell surface. Knock down of CRT and/or ERP57 suppressed the phagocytosis of anthracyclines-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. The anthracyclines-induced CRT and/or ERP57 translocation was mimicked by inhibition of the protein phosphatase 1/GADD34 complex. Administration of recombinant calreticulin, and not recombinant ERP57, or inhibitors of protein phosphatase 1 /GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify calreticulin and/or ERP57 as a key feature determining anti-cancer immune responses and delineate a possible strategy for immunogenic chemotherapy. This invention demonstrates that calreticulin exposure dictates also sperm-egg fusion. This invention includes also the using of recombinant CRT and/or ERP57 or the inducers of the translocation of CRT and/or ERP57 protein to treat sterility. The detection of the translocation of CRT and/or ERP57 is a good way to screen new immunogenic molecules and compounds.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/882,183 US20110060120A1 (en) | 2006-09-08 | 2010-09-14 | Immunogenic treatment of cancer by peptides inducing the plasma membrane exposure of erp57 |
Applications Claiming Priority (22)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06291427A EP1900375A1 (en) | 2006-09-08 | 2006-09-08 | Calreticulin for its use as a medication for the treatment of cancer in a mammal |
EP06291427.0-2107 | 2006-09-08 | ||
US11/774,585 | 2007-07-07 | ||
US11/774,585 US20090005302A1 (en) | 2006-09-08 | 2007-07-07 | Method, apparatus, and compound for effecting localized, non-systemic, immunogenic treatment of cancer |
US11/845,065 US20090004134A1 (en) | 2006-09-08 | 2007-08-25 | Kit for treating a health condition by inducing translocation of an erp57 protein to a cellular membrane |
US11/845,063 US20090004178A1 (en) | 2006-09-08 | 2007-08-25 | Pharmaceutical compound for blocking the crt or erp57 translocation |
US11/845,061 US20090004211A1 (en) | 2006-09-08 | 2007-08-25 | Method for effecting localized, non-systemic and systemic, immunogenic treatment of cancer using erp57 translocation |
US11/845,062 US20090010952A1 (en) | 2006-09-08 | 2007-08-25 | Pharmaceutical compound for effecting localized, non-systemic and systemic, immunogenic treatment of cancer using crt or erp57 translocation |
US11/845,067 US20090005305A1 (en) | 2006-09-08 | 2007-08-25 | Service for effecting localized, non-systemic and systemic, immunogenic treatment of cancer using crt translocation |
US11/845,064 | 2007-08-25 | ||
US11/845,060 US20080214452A1 (en) | 2006-09-08 | 2007-08-25 | Method for effecting localized, non-systemic and systemic, immunogenic treatment of cancer using crt translocation |
US11/845,067 | 2007-08-25 | ||
US11/845,065 | 2007-08-25 | ||
US11/845,061 | 2007-08-25 | ||
US11/845,063 | 2007-08-25 | ||
US11/845,060 | 2007-08-25 | ||
US11/845,064 US20090048159A1 (en) | 2006-09-08 | 2007-08-25 | Kit for treating a health condition by inducing translocation of a calreticulin protein to a cellular membrane |
US11/845,062 | 2007-08-25 | ||
US11/845,069 US20090004678A1 (en) | 2006-09-08 | 2007-08-26 | Method for screening fertility and new compounds or molecules, using crt or erp57 translocation |
US11/845,069 | 2007-08-26 | ||
US11/845,068 US20090004172A1 (en) | 2006-09-08 | 2007-08-26 | Service for effecting localized, non-systemic and systemic, immunogenic treatment of cancer using erp57 translocation |
US11/845,068 | 2007-08-26 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2008032153A2 WO2008032153A2 (en) | 2008-03-20 |
WO2008032153A3 true WO2008032153A3 (en) | 2008-11-27 |
Family
ID=39184169
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2007/002502 WO2008032153A2 (en) | 2006-09-08 | 2007-08-31 | Calreticulin for its use as a medication for the treatment of cancer in a mammal |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2008032153A2 (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2503997B1 (en) | 2009-11-23 | 2017-06-21 | INSERM - Institut National de la Santé et de la Recherche Médicale | Inhibitors of the pp1/gadd34 complex for the treatment of a condition requiring an immunosuppressive activity |
US9801909B2 (en) | 2015-04-06 | 2017-10-31 | The Penn State Research Foundation | Compositions and methods for combating bacterial infections by killing persister cells with mitomycin C |
US10556965B2 (en) | 2016-01-28 | 2020-02-11 | Mayo Foundation For Medical Education And Research | Methods and materials for treating cancer |
CA3061044A1 (en) * | 2017-04-26 | 2018-11-01 | Mayo Foundation For Medical Education And Research | Methods and materials for treating cancer |
CN111766848B (en) * | 2020-06-29 | 2021-09-10 | 北京广利核系统工程有限公司 | Method and device for verifying failure rate of subsystem in instrument control system |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000020577A1 (en) * | 1998-10-06 | 2000-04-13 | The Government Of The United States Of America, Represented By The Secretary, Dept. Of Health And Huuman Services, The National Institutes Of Health | Use of calreticulin and calreticulin fragments to inhibit endothelial cell growth and angiogenesis, and suppress tumor growth |
WO2002006327A2 (en) * | 2000-07-17 | 2002-01-24 | Northwestern University | A method for prognosing cancer and the proteins involved |
WO2002099061A2 (en) * | 2001-06-04 | 2002-12-12 | The Regents Of The University Of Michigan | Method of treating alzheimer's disease with se-containing peptide |
US20030060613A1 (en) * | 1995-01-24 | 2003-03-27 | Shoukat Dedhar | Novel use of calreticulin in modulating hormone responsiveness and new pharmaceuticals for treating cancer, osteoporosis and chronic inflammatory disease |
WO2003068941A2 (en) * | 2002-02-13 | 2003-08-21 | Duke University | Modulation of immune response by non-peptide binding stress response polypeptides |
US20040248217A1 (en) * | 2002-11-01 | 2004-12-09 | Tatsuhiro Yoshiki | Tumor marker for urothelial carcinoma |
-
2007
- 2007-08-31 WO PCT/IB2007/002502 patent/WO2008032153A2/en active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030060613A1 (en) * | 1995-01-24 | 2003-03-27 | Shoukat Dedhar | Novel use of calreticulin in modulating hormone responsiveness and new pharmaceuticals for treating cancer, osteoporosis and chronic inflammatory disease |
WO2000020577A1 (en) * | 1998-10-06 | 2000-04-13 | The Government Of The United States Of America, Represented By The Secretary, Dept. Of Health And Huuman Services, The National Institutes Of Health | Use of calreticulin and calreticulin fragments to inhibit endothelial cell growth and angiogenesis, and suppress tumor growth |
WO2002006327A2 (en) * | 2000-07-17 | 2002-01-24 | Northwestern University | A method for prognosing cancer and the proteins involved |
WO2002099061A2 (en) * | 2001-06-04 | 2002-12-12 | The Regents Of The University Of Michigan | Method of treating alzheimer's disease with se-containing peptide |
WO2003068941A2 (en) * | 2002-02-13 | 2003-08-21 | Duke University | Modulation of immune response by non-peptide binding stress response polypeptides |
US20040248217A1 (en) * | 2002-11-01 | 2004-12-09 | Tatsuhiro Yoshiki | Tumor marker for urothelial carcinoma |
Non-Patent Citations (2)
Title |
---|
GARDAI S.J. ET AL: "Cell-surface calreticulin initiates clearance of viable apoptotic cells through trans-activation of LRP on the phagocyte.", CELL, vol. 123, 21 October 2005 (2005-10-21), pages 321 - 334, XP002432361 * |
JAZOWIECKA-RAKUS J. ET AL.: "Combination of vasotatin gene therapy with cyclophosphamide inhibits growth of B16(F10) melanoma tumours.", ACTA BIOCHIMICA POLONICA, vol. 53, no. 1, January 2006 (2006-01-01), pages 199 - 202, XP002432362 * |
Also Published As
Publication number | Publication date |
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WO2008032153A2 (en) | 2008-03-20 |
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