WO1984001288A1 - Process for extracting tumor necrosis factor from macrophage - Google Patents

Process for extracting tumor necrosis factor from macrophage Download PDF

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Publication number
WO1984001288A1
WO1984001288A1 PCT/JP1982/000400 JP8200400W WO8401288A1 WO 1984001288 A1 WO1984001288 A1 WO 1984001288A1 JP 8200400 W JP8200400 W JP 8200400W WO 8401288 A1 WO8401288 A1 WO 8401288A1
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WO
WIPO (PCT)
Prior art keywords
macrophage
necrosis factor
tumor necrosis
tnf
large scale
Prior art date
Application number
PCT/JP1982/000400
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French (fr)
Japanese (ja)
Inventor
Takeshi Makitsubo
Original Assignee
Takeshi Makitsubo
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 Takeshi Makitsubo filed Critical Takeshi Makitsubo
Priority to AU89565/82A priority Critical patent/AU8956582A/en
Priority to PCT/JP1982/000400 priority patent/WO1984001288A1/en
Publication of WO1984001288A1 publication Critical patent/WO1984001288A1/en

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    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/525—Tumour necrosis factor [TNF]

Definitions

  • a method for extracting tumor necrosis factor (d) by killing and macrophage (a) naturally or artificially (c) the macrophage (a) extracted from the living body.
  • E. Metchnikoff (Ann. Rev. Inst. Pasteur, 13:47, 1899) is a macrophage that is present in the body of all animals phylogenetic from protozoa (Protozoa). It has the property of phagocytosing glutaraldehyde-fixed sheep red blood cells) and refers to cells that are presently recognized in macrophages and have membrane antigens and properties.
  • Tumor necrosis factor Tumor necrosis factor
  • TNF tumor necrosis factor
  • BCG Bacillus-Calmette-Guerin
  • LPS lipopolysaccharide
  • the present invention uses a conventional living body to treat tumor necrosis factor (hereinafter referred to as “necrosis factor”).
  • macrophages removed from living organisms and macrophage cultures that can be cultured and grown are collected or grown in large quantities, and killed or destroyed naturally or artificially without using macrophage stimulating substances (such as BCG).
  • macrophage stimulating substances such as BCG
  • this method makes it easier to obtain more uniform TNF than using TNF that is extracted from a living organism because it uses homogeneous macrophages.Thus, a large amount of TNF can be extracted by using culture-growing macrophages. It is. Furthermore, it is possible to purify highly safe TNF because no harmful substances are used.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Toxicology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

A process for extracting tumor necrosis factor (TNF) easily and uniformly on a large scale, which comprises collecting macrophage from a living body or multiplying culturable macrophage strain on a large scale, and naturally or artificially killing and destroying them without using any macrophage-stimulating substance (for example, BCG). This process enables extraction of more uniform TNF on a large scale than that obtained by conventional processes using a living body (for example, mouse, rabbit, etc.) and contaminated with much impurities (e.g., albumin, globulin, etc.)

Description

明 細 書  Specification
マクロフ 7—ジ （大食細胞） より腫瘍壊死因子の抽出法 技 術 分 野  Technique for extracting tumor necrosis factor from macrophages (macrophages)
生体より取り出したマクロファージ （a) を自然 （b) にあるい は人為的 （c) に死滅及び破壌することにより腫瘍壊死因子 （d) を 抽出する方法。  A method for extracting tumor necrosis factor (d) by killing and macrophage (a) naturally or artificially (c) the macrophage (a) extracted from the living body.
(a) 原生動物 （Protozoa) より系統発生した全ての動物の体内に 存在し E. Metchnikoff (Ann. Rev. Inst. Pasteur, 13:47,1899) がマクロファージと命名したもので、 異物 （例え ばグルタールアルデヒド固定羊赤血球のようなもの） を貪食す る特性があり、 現在マクロファージに認められて 、る膜抗原及 び性質を有した細胞を言う。  (a) E. Metchnikoff (Ann. Rev. Inst. Pasteur, 13:47, 1899) is a macrophage that is present in the body of all animals phylogenetic from protozoa (Protozoa). It has the property of phagocytosing glutaraldehyde-fixed sheep red blood cells) and refers to cells that are presently recognized in macrophages and have membrane antigens and properties.
( b ) 培養液を交換しない時などにおこる死滅等を言う。  (b) Killing that occurs when the culture medium is not replaced.
( c ) 腫瘍壊死因子を得る目的でマクロファージを凍結融解をくり返 す方法や超音波処理、 その他何らかの物理的、 化学的方法で死 滅及び破壊することを言う。  (c) To kill and destroy macrophages by repeated freezing and thawing, sonication, or any other physical or chemical method to obtain tumor necrosis factor.
(d) E. A. Carswell L. J. Old (Immunology 72:  (d) E.A.Carswell L.J.Old (Immunology 72:
3666,1975) らによって報告された腫瘍壊死因子 （Tumor necrosis factonTNF) と同等の効果を示すものを言う。 同 等の効果とは、 腫瘍細胞を死滅させるが正常細胞には有害な影 響を及ぼさない効果を言う。  3666, 1975) and others that show the same effect as the tumor necrosis factor (Tumor necrosis factonTNF). Equivalent effects are those that kill tumor cells but do not have a detrimental effect on normal cells.
背 景 技 術 Background technology
従来、 腫瘍壌死因子 （以下 TNFと略す） は生体 （例えば実験動 物、 マウス、 ゥサギ等） に BCG (bacillus— Calmette—Guerin) を接取し 14日後に菌体内毒素である LPS (lipopolysaccharide W from Escherichia coli) を静脈注射して 2時間後に全採血 し、 得られた血清中に含まれたかたちで抽出されていた。 また大量に 得るには何匹もの動物が必要で、 そのため一匹一匹から得られる T N Fの含有率が不均一であった。 しかも血清中に存在するため他の蛋白 (例えばアルブミン、 グロブリン等） が多く、 精製するには非常に複 雑な過程と時間を要し、 さらに最終的に得られた T N Fは決して多く はなかった。 このような背景から、 より均一で容易にしかも大量に T N Fを抽出する方法が望まれている。 Conventionally, tumor necrosis factor (hereinafter abbreviated as TNF) is obtained by contacting BCG (bacillus-Calmette-Guerin) to living organisms (eg, experimental animals, mice, and egrets), and 14 days later, LPS (lipopolysaccharide), an intracellular toxin. W from Escherichia coli) was injected intravenously and two hours later, the whole blood was collected and extracted as contained in the serum obtained. Many animals were required to obtain large quantities, and the TNF content obtained from each animal was heterogeneous. In addition, since it is present in serum, it contains many other proteins (eg, albumin, globulin, etc.), and purification requires a very complicated process and time. . Against this background, there is a need for a method for extracting TNF more uniformly, easily and in large quantities.
発 明 の 開示 Disclosure of the invention
この発明 （方法） は、 従来の生体を使用して腫瘍壊死因子 （以下 The present invention (method) uses a conventional living body to treat tumor necrosis factor (hereinafter referred to as “necrosis factor”).
T N Fと略す） を得る方法よりも、 容易にしかも大量に均一な T N F を得ることを目的としている。 It is intended to obtain a uniform TNF easily and in a large amount, rather than a method of obtaining the TNF.
すなわち生体から取り出したマクロファージ及び培養増殖が可能 なマクロファージ培養株を大量に採取または大量に増殖させマクロフ ァージ刺激物質 （例えば B C Gなど） 等を使用することなく自然にあ るいは人為的に死滅及び破壊することによって、 その培養上清 （培養 液） 中に TN Fが多量に含まれていることを見出した。  In other words, macrophages removed from living organisms and macrophage cultures that can be cultured and grown are collected or grown in large quantities, and killed or destroyed naturally or artificially without using macrophage stimulating substances (such as BCG). As a result, it was found that a large amount of TNF was contained in the culture supernatant (culture solution).
したがつてこの方法は、 均一なマクロファージを使用するため生 体から抽出する T NFより、 より均一な T N Fが得られやすく培養増 殖性マクロファージを使用することによって大量に T N Fを抽出する ことが可能である。 さらに生体に有害な物 ¾を使用しな 、ため安全性 の高い T NFを精製することが出来る。  Therefore, this method makes it easier to obtain more uniform TNF than using TNF that is extracted from a living organism because it uses homogeneous macrophages.Thus, a large amount of TNF can be extracted by using culture-growing macrophages. It is. Furthermore, it is possible to purify highly safe TNF because no harmful substances are used.
産業上の利用可能性 Industrial applicability
この方法 (発明）はマク口ファージ特に培養増殖可能なマクロファ ージ株が得られれば、非常に容易に腫瘍壤死因子の量産が可能である。  According to this method (invention), it is possible to mass-produce tumor soil death factor very easily if a macophage phage, particularly a macrophage strain that can be cultured and propagated, is obtained.

Claims

請 求 の 範 囲 The scope of the claims
1. 生体より取り出したマクロファージの性状を有する細胞及び細胞 集団を自然にあるいは人為的に死滅及び破壊することによつて腫瘍 壊死因子を抽出する方法。  1. A method for extracting tumor necrosis factor by killing or destroying cells or cell populations having the properties of macrophages taken out of a living body, either naturally or artificially.
PCT/JP1982/000400 1982-10-06 1982-10-06 Process for extracting tumor necrosis factor from macrophage WO1984001288A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU89565/82A AU8956582A (en) 1982-10-06 1982-10-06 Process for extracting tumor necrosis factor from macrophage
PCT/JP1982/000400 WO1984001288A1 (en) 1982-10-06 1982-10-06 Process for extracting tumor necrosis factor from macrophage

Applications Claiming Priority (1)

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PCT/JP1982/000400 WO1984001288A1 (en) 1982-10-06 1982-10-06 Process for extracting tumor necrosis factor from macrophage

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WO (1) WO1984001288A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2158829B (en) * 1984-04-06 1992-04-22 Asahi Chemical Ind Human tumor necrosis factor and dna therefor
US5487984A (en) * 1984-12-21 1996-01-30 Biogen, Inc. Processes for producing tumor necrosis factor

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57140726A (en) * 1981-12-28 1982-08-31 Dainippon Pharmaceut Co Ltd Purification of physiologically active substance having carcinostatic action
JPS57140725A (en) * 1981-12-28 1982-08-31 Dainippon Pharmaceut Co Ltd Physiologically active substance having carcinostatic action

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57140726A (en) * 1981-12-28 1982-08-31 Dainippon Pharmaceut Co Ltd Purification of physiologically active substance having carcinostatic action
JPS57140725A (en) * 1981-12-28 1982-08-31 Dainippon Pharmaceut Co Ltd Physiologically active substance having carcinostatic action

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2158829B (en) * 1984-04-06 1992-04-22 Asahi Chemical Ind Human tumor necrosis factor and dna therefor
US5487984A (en) * 1984-12-21 1996-01-30 Biogen, Inc. Processes for producing tumor necrosis factor

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Publication number Publication date
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