EP1986664A4 - Composition anticancéreuse comprenant un oligonucléotide et des lipopolysaccharides (lps) non toxiques - Google Patents

Composition anticancéreuse comprenant un oligonucléotide et des lipopolysaccharides (lps) non toxiques

Info

Publication number
EP1986664A4
EP1986664A4 EP06715813A EP06715813A EP1986664A4 EP 1986664 A4 EP1986664 A4 EP 1986664A4 EP 06715813 A EP06715813 A EP 06715813A EP 06715813 A EP06715813 A EP 06715813A EP 1986664 A4 EP1986664 A4 EP 1986664A4
Authority
EP
European Patent Office
Prior art keywords
cia05
odn
cancer
lipopolysaccharide
coli
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Withdrawn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
EP06715813A
Other languages
German (de)
English (en)
Other versions
EP1986664A1 (fr
Inventor
Bo-Young Ahn
Yang-Je Cho
Won-Il Yoo
Na-Gyong Lee
Doo-Sik Kim
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.)
Daewoong Pharmaceutical Co Ltd
Eyegene Inc
Original Assignee
Daewoong Pharmaceutical Co Ltd
Eyegene Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Daewoong Pharmaceutical Co Ltd, Eyegene Inc filed Critical Daewoong Pharmaceutical Co Ltd
Publication of EP1986664A1 publication Critical patent/EP1986664A1/fr
Publication of EP1986664A4 publication Critical patent/EP1986664A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • 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
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/739—Lipopolysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to an anti-cancer drug using an LPS-derived
  • CIA05 non-toxic high molecular compound
  • ODNs oligodeoxynucleotides
  • Non-specific immunotherapy is the most spotlighted immunotherapy which has
  • the non-specific immunotherapy it is meant that the immunotherapy is irrespective of the kinds of the cancers by expression. And, many theories concerning its intrinsic mechanisms have been proposed until now, but the
  • lymphocytes and there is a point of action in an aspect of the immunological
  • Corynebacterium has been actually used as a leading material in clinical
  • Coley' s mixed toxin is composed of substances extracted from the Streptococci medium
  • DNAs is the significant CpG suppression and the selective methylation of CpG
  • CpG dinucleotides is not associated with an anti-cancer effect, and it is also reported
  • LPS is a typical thymus-independent antigen which
  • LPS can use its toxicity to kill cancer cells, and its subunit Lipid A especially shows an anti-cancer effect by inducing
  • the present invention is designed to solve the problems of the prior art, and therefore it is an object of the present invention to provide a substance capable
  • the present invention provides an
  • anti-cancer drug including oligodeoxynucleotides (ODNs) and bacterial LPS-derived
  • the non-toxic compound preferably has a molecular weight
  • the ODNs and the bacterial LPS-derived non-toxic bacteria are also present invention. Also in the present invention, the ODNs and the bacterial LPS-derived non-toxic
  • the two components are preferably mixed by shaking.
  • T helper type 1 cells immunoactivation of T helper type 1 cells and activation of NK cells.
  • the bacterium, used in the present invention is preferably Escherichia coli
  • mycobacteria or mycobacteria, and more preferably Escherichia coli.
  • FIG. 1 is an electrophoretic diagram showing separated products of
  • the diagram shows the separated products of the lipopolysaccharides in 5 batch experiments, respectively.
  • FIG. 2 is an electrophoretic diagram showing that Lipid A is degraded by
  • lane 1 represents a marker
  • lane 2 represents separated products of lipopolysaccharides (CIA04), and lane 3
  • CIA05 alkaline-treated non-toxic lipopolysaccharides
  • FIG. 3 is a diagram showing that an amount of TNF- ⁇ secreted in THP-I
  • THP-I cells to secrete a large amount of TNF- ⁇ , while the non-toxic CIA05 induces
  • FIG. 4 is a diagram showing, from an amount of IL- 12 expressed in human
  • ODNs oligodeoxynucleotides
  • FIG. 5 is a diagram showing, from an amount of IL- 12 expressed in human
  • ni7909 represents
  • FIG. 6 is a diagram showing that immunity of the ODN having phosphorothioate is improved by CIA05.
  • 7909(s) represents the phosphorothioate form ODN
  • FIG. 7 is a graph showing an anticancer effect of the ODN by the CIA05 in a
  • the inventors designed a bacterial LPS-derived non-toxic high-molecular
  • lipopolysaccharides to participate in various reactions, for example by acting as a T
  • the inventors screened a strain (E. coli EG0021) having a very short sugar chain
  • accession number was KCCM 10374. And, there was established a method for
  • CIA05 which is very safe and shows an anti-cancer effect.
  • ODNs oligodeoxynucleotides
  • ODN 1826 TCCATGACGTTCCTGACGTT (SEQ ID NO: 1; 20 mer)
  • the strain E. coli EG0021 having a very short sugar chain of lipopolysaccharides having a very short sugar chain of lipopolysaccharides
  • a human lymphocyte cell line differentiated with GM-CSF was
  • TNF- ⁇ was selected (Table 1), and a molecular weight of the lipopolysaccharide was
  • cytocine residues of CG sequences were selectively methylated with Sss I methyalse.
  • DNA methylation was carried out by mixing 1 unit of CpG methylase (M. Sss I;
  • SAM S-adenosylmethionine
  • the strain E. coli was prepared in the same manner as in the DNA separation.
  • the strain prepared thus was mixed with 2 X volumes of ethanol, centrifuged
  • the resultant mixture was divided into glass centrifuge tubes and centrifuged at
  • lipopolysaccharides was measured, normalized as a standard to measure its
  • the lipopolysaccharide has a molecular weight of about 3,000 to
  • lipopolysaccharide was degraded by the alkaline treatment, and therefore was smaller
  • THP-I acute monocytic leukemia
  • a vaccine was intravenously injected into the rabbit ears at an amount of 0.2
  • thermometer ⁇ g/ ⁇ mi per 1 kg of a rabbit, and then each thermometer was inserted into their recta
  • thermometer which
  • thermometer into a rectum at the constant depth of 60 mm to 90 mm, and checking its
  • the temperature after a predetermined time was used as a control temperature.
  • the sample pre-warmed to about
  • control temperature was measured.
  • the body temperature was checked very 3 hours, at leased every 1 hour after injection.
  • a difference of the measured temperatures and the control body temperature was calculated, and the difference was referred to as a
  • pyrogen test is considered to be "negative", while if it is 2.5 ° C or more, a pyrogen test
  • Venous blood was aseptically taken from healthy adult males, and put into a vacuum tube including an anti-coagulant heparin. The resultant whole blood was
  • ODN oligodeoxynucleotide
  • CG-free ODN (nonCG) showed a similar immune-stimulating effect to that of saline used as the control if it was used alone, but showed a strong immune-stimulating effect
  • ODN That is, the ODN (m7909) methylated at a cytosine residue of a GC sequence
  • 7909(s) is a oligodeoxynucleotide in which a diester
  • the tumor cell line was
  • the tumor cell line was administered into right flanks of the C3H/HeJ mice, and a
  • CIA05 on the treatment of the bladder cancer was determined by measuring a
  • bladder cancer cell line was administered subcutaneously into right flanks of the
  • CIA07 was administered subcutaneously into the same site that the tumor cell line was
  • the bacteria-derived substance (CIA05) of the present invention may induce
  • oligodeoxynucleotide used alone as the therapeutic agent.
  • the E. co//-derived anti-cancer drug of the present invention may be any E. co//-derived anti-cancer drug of the present invention. Accordingly, the E. co//-derived anti-cancer drug of the present invention may be any E. co//-derived anti-cancer drug of the present invention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une composition anticancéreuse comprenant comme principes actifs des oligodésoxynucléotides et des lipopolysaccharides non toxiques dérivés de LPS.
EP06715813A 2006-02-01 2006-02-01 Composition anticancéreuse comprenant un oligonucléotide et des lipopolysaccharides (lps) non toxiques Withdrawn EP1986664A4 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR2006/000360 WO2007089051A1 (fr) 2006-02-01 2006-02-01 Composition anticancéreuse comprenant un oligonucléotide et des lipopolysaccharides (lps) non toxiques

Publications (2)

Publication Number Publication Date
EP1986664A1 EP1986664A1 (fr) 2008-11-05
EP1986664A4 true EP1986664A4 (fr) 2009-07-22

Family

ID=38327599

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06715813A Withdrawn EP1986664A4 (fr) 2006-02-01 2006-02-01 Composition anticancéreuse comprenant un oligonucléotide et des lipopolysaccharides (lps) non toxiques

Country Status (3)

Country Link
EP (1) EP1986664A4 (fr)
CN (1) CN101394857A (fr)
WO (1) WO2007089051A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL2444103T3 (pl) * 2009-06-19 2018-05-30 Eyegene Inc. Szczepionka przeciwko rakowi szyjki macicy

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004039413A1 (fr) * 2002-05-22 2004-05-13 Eyegene Inc Composition de controle et de simulation immunitaire contenant des fragments d'adn chromosomal bacterien et des lipopolysaccharides non toxiques
WO2006121232A1 (fr) * 2005-05-10 2006-11-16 Eyegene Inc. Adjuvant comprenant un oligonucleotide et des lps non toxiques

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CU23178A1 (es) * 2002-04-15 2006-09-22 Ct Ingenieria Genetica Biotech INMUNOTERAPIA ACTIVA ANTIANGIOGéNICA
CA2388049A1 (fr) * 2002-05-30 2003-11-30 Immunotech S.A. Oligonucleotides immunostimulateurs et utilisations connexes
AR040996A1 (es) * 2002-08-19 2005-04-27 Coley Pharm Group Inc Acidos nucleicos inmunoestimuladores

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004039413A1 (fr) * 2002-05-22 2004-05-13 Eyegene Inc Composition de controle et de simulation immunitaire contenant des fragments d'adn chromosomal bacterien et des lipopolysaccharides non toxiques
WO2006121232A1 (fr) * 2005-05-10 2006-11-16 Eyegene Inc. Adjuvant comprenant un oligonucleotide et des lps non toxiques

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
GAO J J ET AL: "BACTERIAL DNA AND LIPOPOLYSACCHARIDE INDUCE SYNERGISTIC PRODUCTION OF TNF-ALPHA THROUGH A POST-TRANSCRIPTIONAL MECHANISM", JOURNAL OF IMMUNOLOGY, AMERICAN ASSOCIATION OF IMMUNOLOGISTS, US, vol. 166, no. 11, 1 June 2001 (2001-06-01), pages 6855 - 6860, XP001206755, ISSN: 0022-1767 *
GAO J J ET AL: "CUTTING EDGE: BACTERIAL DNA AND LPS ACT IN SYNERGY IN INDUCING NITRIC OXIDE PRODUCTION IN RAW 264.7 MACROPHAGES", JOURNAL OF IMMUNOLOGY, AMERICAN ASSOCIATION OF IMMUNOLOGISTS, US, vol. 163, no. 8, 15 October 1999 (1999-10-15), pages 4095 - 4099, XP001206756, ISSN: 0022-1767 *
HUANG HONG ET AL: "[The synergistic effects of lipopolysaccharide, bacterial lipoprotein and bacterial DNA on mouse alveolar macrophage activation]", ZHONGHUA YI XUE ZA ZHI 8 JUN 2005, vol. 85, no. 21, 8 June 2005 (2005-06-08), pages 1468 - 1472, XP002530641, ISSN: 0376-2491 *
See also references of WO2007089051A1 *
YI ET AL: "CpG DNA synergize for tumor necrosis factor-a production through activation of NF-kB", INTERNATIONAL IMMUNOLOGY, OXFORD UNIVERSITY PRESS, GB, vol. 13, no. 11, 1 November 2001 (2001-11-01), pages 1391 - 1404, XP002986604, ISSN: 0953-8178 *

Also Published As

Publication number Publication date
WO2007089051A1 (fr) 2007-08-09
CN101394857A (zh) 2009-03-25
EP1986664A1 (fr) 2008-11-05

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