EP1409534A2 - Composition pharmaceutique pour assurer le traitement et la prophylaxie de tumeurs chez l'homme, qui expriment l'antigene tumoral mucine et/ou l'antigene carcino-embryonnaire et son utilisation - Google Patents

Composition pharmaceutique pour assurer le traitement et la prophylaxie de tumeurs chez l'homme, qui expriment l'antigene tumoral mucine et/ou l'antigene carcino-embryonnaire et son utilisation

Info

Publication number
EP1409534A2
EP1409534A2 EP00982945A EP00982945A EP1409534A2 EP 1409534 A2 EP1409534 A2 EP 1409534A2 EP 00982945 A EP00982945 A EP 00982945A EP 00982945 A EP00982945 A EP 00982945A EP 1409534 A2 EP1409534 A2 EP 1409534A2
Authority
EP
European Patent Office
Prior art keywords
gene
human
pharmaceutical composition
therapeutic
cea
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP00982945A
Other languages
German (de)
English (en)
Inventor
Gabriele Pecher
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
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
Application filed by Individual filed Critical Individual
Publication of EP1409534A2 publication Critical patent/EP1409534A2/fr
Withdrawn legal-status Critical Current

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
    • C07K14/46—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
    • C07K14/4727—Mucins, e.g. human intestinal mucin
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

Definitions

  • compositions for the treatment and prophylaxis of human tumors which express the tumor antigen mucin and / or the carcinoembryonic antigen (CEA) and their use
  • the invention relates to a pharmaceutical composition for the treatment and prophylaxis of human tumors which express the tumor antigen mucin and / or the carcinoembryonic antigen (CEA), and their use as a vaccine in humans for activating the immune system.
  • CEA carcinoembryonic antigen
  • the vaccines are designed to activate the immune system so that the tumors and / or their metastases are specifically combated.
  • the classic and widely used vaccine consists of a mixture of irradiated tumor cells and adjuvants, e.g. BCG. After about two decades of clinical trials, it can be summarized that this vaccine is not sufficiently effective (see Oettgen H. and Old L., The History of Cancer Immunotherapy in: Biological Therapy of Cancer, Eds. V. deVita, S. Hellmann and S. Rosenberg, JB Lippincott Company 1991, pp. 87-119).
  • a pharmaceutical composition which has a plasmid ("naked DNA") which as a therapeutic gene contains the human Muzingen MUCl, active fragments thereof or at least 3 repeats of the amino acid sequence SEQ No. 1 according to FIG. 1, and / or another plasmid ("naked DNA") which, as a therapeutic gene, contains the gene for the human carcinoembryonic antigen (CEA) SEQ No. 2 as shown in Figure 2.
  • naked DNA plasmid
  • CEA human carcinoembryonic antigen
  • the pharmaceutical composition is preferably provided as a vaccine and, depending on the respective tumor, the plasmids with the respective therapeutic gene are applied either individually or together.
  • the pharmaceutical composition is a combination preparation and contains at least one of the above-mentioned plasmids with the respective therapeutic gene mentioned and also at least one recombinant adenovirus, the two therapeutic genes, namely the human mucin gene MUCl, effective fragments thereof or at least 3 repeats of the amino acid sequence SEQ No. 1 and has the gene for human interleukin 12.
  • this adenovirus is replaced or combined with another recombinant adenovirus which also has two therapeutic genes, namely the gene for the human carcinoembryonic antigen (CEA) SEQ No. 2 and the gene for human interleukin 12.
  • CEA human carcinoembryonic antigen
  • the combination according to the invention of plasmids which have the respective therapeutic gene with the effective therapeutic genes packaged in adenoviruses represents an effective vaccine system.
  • the effectiveness thereof may be increased by the combination with a vaccinia virus, which also contains a corresponding therapeutic gene.
  • the pharmaceutical composition according to the invention therefore additionally has a recombinant vaccina virus which, as a therapeutic gene, also contains the human mucin gene MUCl, active fragments thereof or at least 3 repeats of the amino acid sequence SEQ No. 1 contains, which in turn is replaced or combined with another recombinant vaccina virus, which as the therapeutic gene is the gene for human Carcinoembryonic Antigen (CEA) SEQ No 2 contains
  • CEA Carcinoembryonic Antigen
  • the plasmids, adenoviruses and vaccina viruses mentioned with the respective therapeutic genes can also be successfully administered individually and independently of one another and activate the immune system. However, the combination of the components increases the effectiveness many times over
  • the application is made as a combination preparation.
  • the pharmaceutical composition that first applies at least one of the plasmids mentioned, with the therapeutic gene corresponding to the tumor, is applied first after a time interval of at least 6 days, again depending from the tumor, the administration of the adenovirus or both adenoviruses, which have the mentioned therapeutic genes for MUCl and IL12 and or CEA and IL12.
  • the vaccinia viruses again after a period of at least 6 days, the vaccinia viruses, if any, the therapeutic genes mentioned have administered
  • a plasmid which contains fragments of the human mucin gene MUCl (see FIG. 1) which are effective as a therapeutic gene, was produced, likewise a recombinant adenovirus, which also expands muzm (Dose 10 8 pfu) in C57Black / 6 mice 14 days later, 50 ⁇ g of mucin plasmid ("naked" DNA) was administered intramuscularly to the mouse.
  • control mice with a recombinant adenovirus that contained an irrelevant gene (“mock") and after 14 days inoculated with a plasmid, which also contained the irrelevant gene. Further control mice were inoculated with PBS only.
  • mice were given a mouse tumor that expands the human mucin by gene transfer were immunized with the mucin-containing plasmid and adenovirus, the tumor never grew and all animals survived.
  • the T umore an and the animals had to be killed after about 25 days, because the tumor reached a size of 1 cm 3 (see Fig. 3). This shows that vaccination with a recombinant adenovirus, which contains the Muzm gene, and subsequently "naked" Mucin DNA prevented tumor growth

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Toxicology (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une composition pharmaceutique utilisée pour assurer le traitement et la prophylaxie de tumeurs chez l'homme, qui expriment l'antigène tumoral mucine et/ou l'antigène carcino-embryonnaire (CEA), ainsi que son utilisation comme vaccin chez l'homme pour activer le système immunitaire. Selon l'invention, il est prévu une composition pharmaceutique comportant un plasmide ( </= ADN nu >/= ) contenant comme gène thérapeutique le gène de mucine humain MUC1, des fragments actifs dudit gène ou au moins trois séquences répétées de la séquence d'aminoacide SEQ n DEG 1 et/ou un autre plasmide ( </= ADN nu >/= ) qui contient comme gène thérapeutique le gène de l'antigène carcino-embryonnaire humain (CEA) SEQ n DEG 2.
EP00982945A 1999-09-27 2000-09-26 Composition pharmaceutique pour assurer le traitement et la prophylaxie de tumeurs chez l'homme, qui expriment l'antigene tumoral mucine et/ou l'antigene carcino-embryonnaire et son utilisation Withdrawn EP1409534A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19948105 1999-09-27
DE19948105 1999-09-27
PCT/DE2000/003443 WO2001024832A2 (fr) 1999-09-27 2000-09-26 Composition pharmaceutique pour assurer le traitement et la prophylaxie de tumeurs chez l'homme, qui expriment l'antigene tumoral mucine et/ou l'antigene carcino-embryonnaire et son utilisation

Publications (1)

Publication Number Publication Date
EP1409534A2 true EP1409534A2 (fr) 2004-04-21

Family

ID=7924664

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00982945A Withdrawn EP1409534A2 (fr) 1999-09-27 2000-09-26 Composition pharmaceutique pour assurer le traitement et la prophylaxie de tumeurs chez l'homme, qui expriment l'antigene tumoral mucine et/ou l'antigene carcino-embryonnaire et son utilisation

Country Status (4)

Country Link
EP (1) EP1409534A2 (fr)
AU (1) AU1991901A (fr)
DE (1) DE10048710A1 (fr)
WO (1) WO2001024832A2 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6949629B2 (en) 2002-03-13 2005-09-27 Aspenbio, Inc. Methods for purifying selected CEA family member proteins
WO2005046622A2 (fr) * 2003-11-12 2005-05-26 Therion Biologics Corporation Vecteurs adaptes servant au traitement et a la prevention du cancer du pancreas
DK1694364T3 (da) * 2003-11-12 2014-07-21 Us Government System til behandling og forebyggelse af brystcancer
JP5148116B2 (ja) 2004-02-11 2013-02-20 イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・エルレ・エルレ 癌胎児性抗原融合タンパク質及びその使用
NZ576360A (en) 2006-11-24 2011-07-29 Tigenix Nv Marker genes for use in the identification of chondrocyte phenotypic stability and in the screening of factors influencing cartilage production
EP3184548A1 (fr) * 2015-12-23 2017-06-28 Miltenyi Biotec GmbH Récepteur d'antigène chimérique avec activation de récepteur de cytokine ou domaine de blocage

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69519521T2 (de) * 1994-10-03 2001-06-28 Us Gov Nat Inst Health Zusammensetzung enthaltend ein antigen exprimierendes rekombinantes virus und ein immunstimulierendes molekül exprimierendes rekombinantes virus
DE19516673A1 (de) * 1995-04-28 1996-10-31 Gabriele Dr Pecher Vakzine gegen Tumorerkrankungen
EP0906444A1 (fr) * 1996-04-19 1999-04-07 Gabriele Pecher Cellules dendritiques humaines genetiquement transfectees, leur production et leur utilisation, de preference comme vaccins
DE19617837A1 (de) * 1996-04-19 1997-10-23 Gabriele Dr Pecher Dendritische Zellen transfiziert mit Muzin-cDNA als Vakzine gegen humane Tumorerkrankungen
CA2354024C (fr) * 1998-12-09 2009-12-22 Jeffrey Schlom Vecteur recombine exprimant des molecules costimulantes multiples et leurs utilisations

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0124832A3 *

Also Published As

Publication number Publication date
DE10048710A1 (de) 2001-10-04
AU1991901A (en) 2001-05-10
WO2001024832A2 (fr) 2001-04-12
WO2001024832A3 (fr) 2002-04-18

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