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WO1992004887A1 - Production de lymphocites t cytotoxiques - Google Patents

Production de lymphocites t cytotoxiques Download PDF

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Publication number
WO1992004887A1
WO1992004887A1 PCT/JP1990/001231 JP9001231W WO9204887A1 WO 1992004887 A1 WO1992004887 A1 WO 1992004887A1 JP 9001231 W JP9001231 W JP 9001231W WO 9204887 A1 WO9204887 A1 WO 9204887A1
Authority
WO
WIPO (PCT)
Prior art keywords
antigen
liposome
complex
coated
protein
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.)
Ceased
Application number
PCT/JP1990/001231
Other languages
English (en)
Japanese (ja)
Inventor
Junzo Sunamoto
Hiroshi Shiku
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.)
KH Neochem Co Ltd
Original Assignee
Kyowa Hakko Kogyo Co Ltd
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 Kyowa Hakko Kogyo Co Ltd filed Critical Kyowa Hakko Kogyo Co Ltd
Priority to PCT/JP1990/001231 priority Critical patent/WO1992004887A1/fr
Publication of WO1992004887A1 publication Critical patent/WO1992004887A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K39/12—Viral antigens
    • A61K39/21—Retroviridae, e.g. equine infectious anemia virus
    • 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
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
    • A61K47/6911—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
    • 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
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
    • C12N2740/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16211—Human Immunodeficiency Virus, HIV concerning HIV gagpol
    • C12N2740/16234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • the present invention relates to a cancer cell antigen or a virus antigen-ribosome complex coated with a polysaccharide containing mannose and a cancer cell or virus antigen using the complex.
  • the present invention relates to a method for inducing a novel cytotoxic T cell (hereinafter abbreviated as “CT”), and a method for treating or preventing cancer or a virus disease using the CTL.
  • CT novel cytotoxic T cell
  • CTL specifically recognizes and impairs cancer cells or virus- and virus-sensitized cells by their antigen receptors, and CTLs are used to detect in vivo cancer or virus. It is also known to be important in host defense mechanisms against Luss.
  • the present invention provides a cancer cell antigen or a virus antigen-liposome complex, which is coated with a polysaccharide containing mannose.
  • antigen refers to substances that elicit an immune response, such as polypeptides, polypeptide complexes, glycoproteins, nucleic acids, and the like. It may be part of the pathological target itself, or may be an antigen expressed by a diseased tissue such as a neoplastic tissue or a virus-infected cell.
  • an antigen protein is preferably used.
  • the antigen protein any origin and purity can be used as long as it includes an antigen determination site, but those prepared by a gene recombination method are preferable.
  • the molecular weight of the antigen protein is not particularly limited as long as it includes at least one antigen-determining site, but is generally 500 to 1,000,000, preferably 200 to 100,000. is there.
  • gag protein and env protein of ATLV include the gag protein and env protein of ATLV, the env protein of HIV, and partial proteins thereof.
  • gag-env fusion protein of ATLV described in the following literature can be mentioned. [JP-A-62-48699; Kuga, T. et al., Japanese 'Journal of Cancer Research., Jpn. J. Cancer Res., 79, 1168-1173 (1988) )].
  • the method of preparing the liposome, the method of encapsulating the antigen in the liposome, and the method of coating the liposome with the Mannos polysaccharide are prepared by the method developed by the present inventors. However, it is also possible to use a general liposome preparation method. [M's Jy's Best Mouth (MJ Ostro), Liposomes, MARCEL DEKER, INC (1987, New York).
  • the mannose-containing polysaccharide may be a chemically synthesized product, a natural extract, or a chemically modified product thereof, as long as mannose is contained as a constituent sugar.
  • readily available mannans and mannan derivatives are used.Particularly, cholesterol residues are partially introduced into mannans for the purpose of producing stable coated polysaccharide ribosomes. It is preferred to do so.
  • JP-A-61-268628 Sunamoto et al., Chem. Lett. 1781 (1988); Takada, A. et al., Biohi Mika. Biochim. Biophys. Acta 802, 237 (1984); Sunamoto, Pathophysiology, 771 (1987)].
  • the liposome can be coated with the mannose-containing polysaccharide by incubating the polysaccharide.ice solution and the liposome at an appropriate temperature.
  • An example of a method for preparing an antigen-liposome complex coated with a mannan derivative is performed by the following procedure. (1) Preparation of liposomes, (2) Modification of liposomes to antigens, (3) Coating of antigen-modified ribosomes with mannan derivatives
  • liposomes formed a bilayer membrane with the same basic structure as cell plasma membrane when Bangham in the United Kingdom redispersed phospholipids derived from natural products in water. Since it was found that it has a Balta structure and closed vesicle morphology, it has been used as a membrane model or as a microcapsule, and it has been reported that the membrane fluidity ⁇ barrier function (membrane permeation barrier) etc. It has been widely used in research on cell structural characteristics and also on research on animal functions of cells such as aggregation and fusion.
  • a liposome having excellent stability and the partial structure of sphingomyelin, which has been developed by the present inventors and is considered to be a kind of boundary lipid in nature, is considered.
  • DDPC j 1.2-dimyristylamide 1.2-dexoxyphosphatidylcholine
  • the above-mentioned liposome is prepared by using various liposome-forming phospholipids and the above-mentioned DDPC, and various methods known per se.
  • lipids for ribosome formation are More specifically, for example, lipids having an amide group capable of forming a hydrogen bond zone in a membrane of lecithin, sphingomyelin, etc. extracted and purified from soybean, egg yolk, etc. And preferably yolk lecithin, dimyristylphosphatidylzircholine (DMPC), etc.
  • a particularly preferred liposome is a combination of yolk lecithin and DDPC It is usually prepared by combining DMPC and DDPC in a ratio of about 4: 6 or 2: 8 (weight ratio).
  • the modification of the antigen to the ribosome is basically performed by simply mixing the two, that is, adding a predetermined amount of the antigen suspension to the ribosome suspension. It can be performed by mixing.
  • the amount of antigen added to the liposome in the above is very important in relation to the ability to express the activity of the obtained complex, and is generally from 10 to L000, preferably about 200 to 10 mg of lecithin in 1 Use the antigen mass.
  • the coating with a mannan derivative is basically performed by simply mixing the two, that is, adding a predetermined amount of a cholesteryl-modified mannan permanent solution to the antigen-modified liposome suspension and mixing.
  • the mass of mannan derivative is 0.1 to 10 mg, preferably about 2 mg per 10 mg of lecithin in 1 mi.
  • antigen-ribosome complex coated with mannose monosaccharide polysaccharide can be used in the present invention as it is, but of course-if necessary, sterilization or the like may be carried out according to a conventional method. Operations can also be performed.
  • the liposome complex of the present invention can be immunized by administering a predetermined value to the animal in the same manner as other conventionally known pectins.
  • the animal to which the vaccine can be applied is not particularly limited, and may be any of various mammals including humans and other animals. Immunization of these animals by administration of the vaccine of the present invention can also be performed according to a general method.
  • the route of administration of the vaccine of the present invention is generally subcutaneous injection, but is not particularly limited thereto.
  • the dose of the pectin of the present invention for the above immunization can be determined as appropriate, but usually the dose is about 50 to: L 50 #g Z ratton times as the antigen. It is appropriate to administer about 1 to 4 times.
  • FIG. 1 shows the results of a comparison of the effect of a mannan-coated antigen-liposome complex on TARS-1 cells.
  • A is a physiological saline
  • B is a mannan-coated antigen-ribosome complex (the present invention)
  • C is a non-mannan-coated antigen-liposome complex
  • D is And the results obtained when the liposomes coated with mannan were respectively administered.
  • FIG. 2 shows a comparison result of induction of CTL activity of the antigen-liposome complex coated with mannan.
  • A is a physiological saline
  • B is a mannan-coated antigen-ribosome complex (the present invention)
  • C is an unmannan-coated antigen-ribosome complex
  • D is a man-ribosome complex.
  • EggPC Egg yolk phosphatid zirconine
  • gag-env fusion protein aqueous solution 1 rafi 200 as protein
  • the gag-env fusion protein aqueous solution 1 rafi 200 as protein
  • the mixture was mixed and incubated at 371: 6 for 6 hours to obtain an antigen-encapsulated liposome suspension 2.
  • physiological saline A in FIG. 1
  • C in FIG. 1 A group was also administered with mannan-coated ribosome alone (D in FIG. 1).
  • Rats were immunized as in Example 2. 1 week after the last dose Later, spleen cells of the test animals were collected. 4 ⁇ 10 7 spleen cells and mitomycin in RPM1 1640 medium 20 ⁇ containing 20% fetal calf serum. 4 x 10 s of the treated TARS-1 cells were co-cultured at 37: for 1 week in a carbon dioxide incubator. The cytotoxicity after culturing was determined by the 51 Cr release method [Nakayama, E. et al., Proc. Of the National University of California, California, Science, USA (Proc. Natl. Acad. Sci. USA) 76, 3486 (1979)] (Fig. 2, B).
  • physiological saline A in FIG. 2
  • an antigen-ribosomal complex not coated with a mannan derivative FOG. 2
  • C ribosome alone coated with a mannan derivative

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Virology (AREA)
  • Dispersion Chemistry (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention se rapporte à un complexe constitué d'un antigène de cellule cancéreuse ou d'un antigène viral associé à un liposome recouvert d'un polysaccharide contenant du mannose, ainsi qu'à un procédé permettant de produire un lymphocite T cytotoxique spécifique à une cellule cancéreuse ou à un antigène viral grâce à l'utilisation dudit complexe.
PCT/JP1990/001231 1990-09-25 1990-09-25 Production de lymphocites t cytotoxiques Ceased WO1992004887A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/JP1990/001231 WO1992004887A1 (fr) 1990-09-25 1990-09-25 Production de lymphocites t cytotoxiques

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/JP1990/001231 WO1992004887A1 (fr) 1990-09-25 1990-09-25 Production de lymphocites t cytotoxiques

Publications (1)

Publication Number Publication Date
WO1992004887A1 true WO1992004887A1 (fr) 1992-04-02

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Application Number Title Priority Date Filing Date
PCT/JP1990/001231 Ceased WO1992004887A1 (fr) 1990-09-25 1990-09-25 Production de lymphocites t cytotoxiques

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WO (1) WO1992004887A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5962437A (en) * 1994-08-29 1999-10-05 Wake Forest University Lipid analogs for treating viral infections
WO2000020563A1 (fr) * 1998-10-02 2000-04-13 Mitsubishi Chemical Corporation Procede d'induction d'une immunite cellulaire et cellules possedant cette immunite
US6656481B1 (en) 1996-09-06 2003-12-02 Mitsubishi Chemical Corporation Vaccinal preparations
JP2004051582A (ja) * 2002-07-23 2004-02-19 Ajinomoto General Foods Inc マンノオリゴ糖を含有する免疫賦活組成物
WO2006104199A1 (fr) * 2005-03-29 2006-10-05 Tokai University Educational System Préparation de liposomes pour l'induction d'une immunité
US7294619B2 (en) 1994-08-29 2007-11-13 Wake Forest University Lipid analogs for inhibiting the activity of hepatitis B antigen
JP2008179563A (ja) * 2007-01-24 2008-08-07 Cosmo Shokuhin Kk 有用リン脂質組成物を含む機能性素材及び機能性食品
WO2008105174A1 (fr) 2007-02-28 2008-09-04 National University Corporation Hokkaido University Liposome utilisé pour induire l'immunité à médiation cellulaire
JP2012232949A (ja) * 2011-05-06 2012-11-29 Osaka Prefecture Univ ｐＨ応答性リポソーム
WO2014034046A1 (fr) 2012-08-27 2014-03-06 国立大学法人帯広畜産大学 Vaccin contre l'infection à toxoplasma gondii
US8821882B2 (en) 2008-09-17 2014-09-02 Obihiro University Of Agriculture And Veterinary Medicine Vaccine preparation for neospora caninum infection

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5126218A (en) * 1974-06-25 1976-03-04 Nat Res Dev Menekikatsuseizaino seiho
JPS57112334A (en) * 1979-12-27 1982-07-13 Fumaan Orutooaniyuaguterumeree Particles of lipid soluble substance, composition consisting of particles and biologically active substance adsorbed with particles and their manufacture
JPS6169801A (ja) * 1984-09-12 1986-04-10 Junzo Sunamoto 天然由来多糖誘導体およびその製造方法
JPS6396560A (ja) * 1986-10-13 1988-04-27 Wako Pure Chem Ind Ltd 固定化方法
JPH01197431A (ja) * 1988-01-30 1989-08-09 Lederle Japan Ltd 感染症治療剤
JPH01233219A (ja) * 1988-03-12 1989-09-19 Nippon Oil & Fats Co Ltd 制癌剤組成物

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5126218A (en) * 1974-06-25 1976-03-04 Nat Res Dev Menekikatsuseizaino seiho
JPS57112334A (en) * 1979-12-27 1982-07-13 Fumaan Orutooaniyuaguterumeree Particles of lipid soluble substance, composition consisting of particles and biologically active substance adsorbed with particles and their manufacture
JPS6169801A (ja) * 1984-09-12 1986-04-10 Junzo Sunamoto 天然由来多糖誘導体およびその製造方法
JPS6396560A (ja) * 1986-10-13 1988-04-27 Wako Pure Chem Ind Ltd 固定化方法
JPH01197431A (ja) * 1988-01-30 1989-08-09 Lederle Japan Ltd 感染症治療剤
JPH01233219A (ja) * 1988-03-12 1989-09-19 Nippon Oil & Fats Co Ltd 制癌剤組成物

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7294621B2 (en) 1994-08-29 2007-11-13 Wake Forest University Lipid analogs for combating tumors
US5962437A (en) * 1994-08-29 1999-10-05 Wake Forest University Lipid analogs for treating viral infections
US7294620B2 (en) 1994-08-29 2007-11-13 Wake Forest University Lipid analogs for inhibiting HIV-1 activity
US7294619B2 (en) 1994-08-29 2007-11-13 Wake Forest University Lipid analogs for inhibiting the activity of hepatitis B antigen
US6656481B1 (en) 1996-09-06 2003-12-02 Mitsubishi Chemical Corporation Vaccinal preparations
WO2000020563A1 (fr) * 1998-10-02 2000-04-13 Mitsubishi Chemical Corporation Procede d'induction d'une immunite cellulaire et cellules possedant cette immunite
JP2004051582A (ja) * 2002-07-23 2004-02-19 Ajinomoto General Foods Inc マンノオリゴ糖を含有する免疫賦活組成物
WO2006104199A1 (fr) * 2005-03-29 2006-10-05 Tokai University Educational System Préparation de liposomes pour l'induction d'une immunité
EA012618B1 (ru) * 2005-03-29 2009-10-30 Токай Юниверсити Эдьюкейшнл Систем Липосомная композиция для индукции иммунитета
JP2008179563A (ja) * 2007-01-24 2008-08-07 Cosmo Shokuhin Kk 有用リン脂質組成物を含む機能性素材及び機能性食品
WO2008105174A1 (fr) 2007-02-28 2008-09-04 National University Corporation Hokkaido University Liposome utilisé pour induire l'immunité à médiation cellulaire
US8821882B2 (en) 2008-09-17 2014-09-02 Obihiro University Of Agriculture And Veterinary Medicine Vaccine preparation for neospora caninum infection
JP2012232949A (ja) * 2011-05-06 2012-11-29 Osaka Prefecture Univ ｐＨ応答性リポソーム
WO2014034046A1 (fr) 2012-08-27 2014-03-06 国立大学法人帯広畜産大学 Vaccin contre l'infection à toxoplasma gondii

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