JPH03128331A - Fine magnetic particle bound antibody and its production - Google Patents
Fine magnetic particle bound antibody and its productionInfo
- Publication number
- JPH03128331A JPH03128331A JP1316576A JP31657689A JPH03128331A JP H03128331 A JPH03128331 A JP H03128331A JP 1316576 A JP1316576 A JP 1316576A JP 31657689 A JP31657689 A JP 31657689A JP H03128331 A JPH03128331 A JP H03128331A
- Authority
- JP
- Japan
- Prior art keywords
- fine particles
- antibody
- magnetic fine
- magnetic particle
- magnetic
- 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.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 239000006249 magnetic particle Substances 0.000 title abstract description 12
- 230000005291 magnetic effect Effects 0.000 claims abstract description 40
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 29
- 201000011510 cancer Diseases 0.000 claims abstract description 25
- 230000001588 bifunctional effect Effects 0.000 claims abstract description 6
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 6
- 230000005294 ferromagnetic effect Effects 0.000 claims abstract description 6
- 239000002245 particle Substances 0.000 claims abstract description 3
- 239000010419 fine particle Substances 0.000 claims description 27
- 238000010438 heat treatment Methods 0.000 abstract description 7
- 229910000889 permalloy Inorganic materials 0.000 abstract description 7
- 206010058467 Lung neoplasm malignant Diseases 0.000 abstract description 4
- 201000005202 lung cancer Diseases 0.000 abstract description 4
- 208000020816 lung neoplasm Diseases 0.000 abstract description 4
- 229910052751 metal Inorganic materials 0.000 abstract description 4
- 239000002184 metal Substances 0.000 abstract description 4
- 238000010521 absorption reaction Methods 0.000 abstract description 3
- 239000000919 ceramic Substances 0.000 abstract description 3
- 206010009944 Colon cancer Diseases 0.000 abstract description 2
- 229910000859 α-Fe Inorganic materials 0.000 abstract description 2
- 206010020843 Hyperthermia Diseases 0.000 abstract 1
- 208000029742 colonic neoplasm Diseases 0.000 abstract 1
- 230000036031 hyperthermia Effects 0.000 abstract 1
- 230000001939 inductive effect Effects 0.000 abstract 1
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 description 5
- 238000000015 thermotherapy Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 238000009217 hyperthermia therapy Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011859 microparticle Substances 0.000 description 3
- 238000013021 overheating Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- JSYGRUBHOCKMGQ-UHFFFAOYSA-N dichloramine Chemical compound ClNCl JSYGRUBHOCKMGQ-UHFFFAOYSA-N 0.000 description 1
- NKSJNEHGWDZZQF-UHFFFAOYSA-N ethenyl(trimethoxy)silane Chemical compound CO[Si](OC)(OC)C=C NKSJNEHGWDZZQF-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000020169 heat generation Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- FZHAPNGMFPVSLP-UHFFFAOYSA-N silanamine Chemical compound [SiH3]N FZHAPNGMFPVSLP-UHFFFAOYSA-N 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Electrotherapy Devices (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、抗体が結合した磁性微粒子およびその製造方
法に関し、特に本発明は、ｔＥ１′ｉ波を吸収して発熱
する磁性微粒子の表面に、癌細胞に選択的に結合する抗
体が結合した磁性微粒子およびその製造方法に関する。Detailed Description of the Invention [Field of Industrial Application] The present invention relates to magnetic fine particles to which antibodies are bound and a method for producing the same. , relates to magnetic particles bound to antibodies that selectively bind to cancer cells, and a method for producing the same.
［従来の技術１
最近、癌の新しい治療方法の一つとして温熱療法が注目
を集めており、種々の加温方法が提案されている０例え
ば、腫瘍の発生箇所が限定されている場合に、その腫瘍
の部分を超音波により又は高周波により局所的に加温す
る温熱療法が知られている。[Prior art 1] Hyperthermia therapy has recently attracted attention as a new treatment method for cancer, and various heating methods have been proposed. For example, when the location of a tumor is limited, Hyperthermia therapy is known in which the tumor area is locally heated using ultrasound or high frequency waves.
また、米国特許４３２３０５６号には、マグネタイトな
どを含有するセラミックスからなる微粒子を腫瘍部分に
注入し、高周波磁場をかけることにより局所的に加温す
る温熱治療法が記載されている。Further, US Pat. No. 4,323,056 describes a thermotherapy method in which fine particles made of ceramics containing magnetite or the like are injected into a tumor area and locally heated by applying a high-frequency magnetic field.
［発明が解決しようとする課題］
しかしながら、従来の加温方法は、いずれも腫瘍の部分
だけを加温してそれ以外の箇所への加熱を避けることは
困難であった。また超音波による温熱療法によって、局
所加温する場合には、照射面積を限定しなければならず
、しかち表皮が過熱されないよう注意することが必要で
あった。一方晶周波による温熱療法においても、表皮付
近が過熱されるのを防止するために電極を冷却すること
が必要であった。[Problems to be Solved by the Invention] However, in all conventional heating methods, it is difficult to heat only the tumor part and avoid heating other parts. Furthermore, when local heating is performed using ultrasonic hyperthermia therapy, the irradiation area must be limited and care must be taken to avoid overheating the epidermis. On the other hand, even in thermotherapy using crystal frequency waves, it is necessary to cool the electrodes to prevent the vicinity of the epidermis from being overheated.
［課題を解決するための手段］
そこで、本発明者等は、上述の如き欠点を解決した温熱
療法を開発すべく鋭意研究した結果、次の如き要旨構成
の磁性微粒子を開発するに到った。[Means for Solving the Problems] Therefore, the present inventors conducted intensive research to develop a thermotherapy that solved the above-mentioned drawbacks, and as a result, they came to develop magnetic fine particles having the following main structure. .
すなわち、本発明は、電磁波を吸収して発熱する磁性微
粒子の表面に、癌細胞に選択的に結合する抗体が結合し
た磁性微粒子、および
磁性微粒子に二官能性架橋剤を結合させた後、これに癌
細胞に選択的に結合する抗体を反応させることを特徴と
する抗体が結合した磁性微粒子の製造方法である。That is, the present invention provides magnetic microparticles to which an antibody that selectively binds to cancer cells is bound to the surface of magnetic microparticles that generate heat by absorbing electromagnetic waves, and a bifunctional cross-linking agent bonded to the magnetic microparticles. This is a method for producing antibody-bound magnetic fine particles, which is characterized by reacting the antibody with an antibody that selectively binds to cancer cells.
なお、前記磁性微粒子は、強ｉｉｎ性微粒子であり、粒
径が５ ｐｍ以下であることが好適である。The magnetic fine particles are ferroin-like fine particles, and preferably have a particle size of 5 pm or less.
本発明における磁性微粒子は、電ｍ波を吸収して磁性微
粒子自体が発熱し、特定の箇所以外を過熱することなく
、温熱療法を行うことができる。The magnetic fine particles in the present invention absorb electromagnetic waves and generate heat themselves, making it possible to perform thermotherapy without overheating areas other than specific areas.
また磁性微粒子の表面に癌細胞に選択的に結合する抗体
を結合させることによって、磁性微粒子を癌細胞に選択
的に集中させることができる。Furthermore, by binding an antibody that selectively binds to cancer cells to the surface of the magnetic particles, the magnetic particles can be selectively concentrated on the cancer cells.
本発明に用いる磁性微粒子としては、電磁波を吸収して
発熱し、人体に無害なちのであれば、使用することがで
きるが、特に人体に吸収されにくい周波数の電磁波を吸
収して発熱するものが有利であり、なかでち強磁性微粒
子は、電磁波の吸収効率が良好で、例えば、フェライト
などのセラミックあるいはパーマロイなどの強磁性金属
等を使用することができる、
前記電磁波としては、高周波磁場を用いることが特に好
ましく、特に電磁波としては、周波数が、ｌＫＨｚ−Ｉ
ＭＨｚの高周波磁場であることが好ましい。１ＫＨｚよ
り高い周波数の高周波磁場が好ましい理由は、磁気ヒ又
テリシス加熱の効率が高いからであり、ＩＭＨｚより低
い周波数の高周波磁場が好ましい理由は、誘導電流によ
る生体の発熱を生起させることなく磁性微粒子を加熱す
ることができるからである。The magnetic fine particles used in the present invention can be used as long as they absorb electromagnetic waves and generate heat and are harmless to the human body, but in particular those that absorb electromagnetic waves at frequencies that are difficult to absorb by the human body and generate heat. Advantageously, the ferromagnetic fine particles have a good absorption efficiency of electromagnetic waves, and for example, ceramics such as ferrite or ferromagnetic metals such as permalloy can be used. The electromagnetic waves use a high frequency magnetic field. It is particularly preferable that the electromagnetic waves have a frequency of 1KHz-I
Preferably, it is a high frequency magnetic field of MHz. The reason why a high-frequency magnetic field with a frequency higher than 1 KHz is preferable is because the efficiency of magnetic hymateresis heating is high, and the reason why a high-frequency magnetic field with a frequency lower than IMHz is preferable is because it can heat the magnetic particles without causing heat generation in the living body due to induced current. This is because it can be heated.
前記高周波磁場の周波数は、なかで０５ Ｋ ｔ−１ｚ
〜２００ＫＨｚの範囲が好適である。The frequency of the high frequency magnetic field is 05 K t-1z
A range of ~200 KHz is preferred.
前記癌細胞に選択的に結合する抗体としては。As the antibody that selectively binds to cancer cells.
例えば、肺癌に対するモノクロナール抗体（ＨＢ４Ｃ５
）、大腸癌に対するモノクロナール抗体（１７−ＬＡ）
、乳癌に対するモノクロナール抗体（Ｈ１５Ｆ２）等を
使用することができる。For example, monoclonal antibodies against lung cancer (HB4C5
), monoclonal antibody against colorectal cancer (17-LA)
, a monoclonal antibody against breast cancer (H15F2), etc. can be used.
ところで、抗体は酵素等と同様に蛋白質の一種であり、
酵素を結合させたマグネタイトがＪｏｕｒｎａｌ ｏｆ
Ｂｉｏｔｅｃｈｎｏｌｏｇｙ ８ （１９８８）、
１３５−１４０に記載されているが、これらのマグ
ネタイトに結合されている酵素は、血栓治療に使用され
るちのであって、本発明の癌細胞に選択的に結合する抗
体とは、全く異なるものであり、しかもマグネタイトは
、前記酵素を体内の目的とする箇所まで外部的な磁力に
よって移動させるためのものであって、本発明の磁性微
粒子とは、目的および効果の点においても全く異なるち
のである。By the way, antibodies, like enzymes, are a type of protein.
Enzyme-bonded magnetite is the Journal of
Biotechnology 8 (1988),
135-140, these magnetite-bound enzymes are used for thrombosis treatment, and are completely different from the antibodies that selectively bind to cancer cells of the present invention. Moreover, magnetite is used to move the enzyme to a target location in the body by external magnetic force, and is completely different from the magnetic fine particles of the present invention in terms of purpose and effect. be.
本発明の抗体が結合した磁性微粒子は次のようにして製
造される。Magnetic particles to which the antibody of the present invention is bound are produced as follows.
磁性微粒子に二官能性架橋剤を結合させた後、これに癌
細胞に選択的に結合する抗体を反応させることにより、
抗体が結合した磁性微粒子を得る。After binding a bifunctional cross-linking agent to magnetic fine particles, this is reacted with an antibody that selectively binds to cancer cells.
Obtain antibody-bound magnetic particles.
前記磁性微粒子が、強磁性金属である場合には、前記強
磁性金属に酸化処理を施して表面に酸化被膜を形成した
後、二官能性架橋剤を結合させることが有利である。When the magnetic fine particles are a ferromagnetic metal, it is advantageous to subject the ferromagnetic metal to an oxidation treatment to form an oxide film on the surface, and then bond the bifunctional crosslinking agent.
前記二官能性架橋剤を結合させる方法としては、例えば
、磁性微粒子にγ−アミノプロピルトリエトキシシラン
およびグルタルアルデヒドを順に結合させる方法、ビニ
ルアルデヒドおよびアクノルアルデヒドを順に結合させ
る方法、あるいはアミノシランおよびポリエチレングリ
コールを順に結合させる方法等を使用することが有利で
ある。Examples of the method for bonding the bifunctional crosslinking agent include a method for sequentially bonding γ-aminopropyltriethoxysilane and glutaraldehyde to magnetic fine particles, a method for sequentially bonding vinylaldehyde and acnoraldehyde, or a method for sequentially bonding aminosilane and polyethylene. It is advantageous to use methods such as sequential coupling of glycols.
［実施例］ 次に、本発明の実施例を詳細に説明する。[Example] Next, embodiments of the present invention will be described in detail.
実施例１
（１）Ｆｅ ３０４・７Ｈ２０の１．６７ｇを水５ｍｌ
！に溶解させ（Ｉ）液とし、硝酸ナトリウムの０．０７
ｇを５−の水に溶解させ（ＩＩ）液とした。（Ｉ）液に
（ＩＩ）液を撹拌しつつ加えて混合溶液とし、この混合
溶液に濃アンモニア水５−をできるだけ早い速度で撹拌
しつつ加えた後、室温で２０分熟成し、平均粒径が０．
６８Ｆ＋のマグネタイトを生成させた。Example 1 (1) 1.67g of Fe 304.7H20 in 5ml of water
! Solution (I) was prepared by dissolving 0.07% of sodium nitrate.
g was dissolved in 5- water to obtain liquid (II). Add liquid (II) to liquid (I) while stirring to form a mixed solution, add concentrated ammonia water 5- to this mixed solution while stirring as fast as possible, and then age at room temperature for 20 minutes. is 0.
68F+ magnetite was produced.
（２）マグネタイトを分離した後、ＮＨ３・水＝５：９
５のアンモニア水２０−で洗浄した。沈澱にオレイン酸
１５０−を加え、１００℃で５分間加熱した後、水を加
えて３０−とじた。(2) After separating magnetite, NH3/water = 5:9
5 and 20 minutes of aqueous ammonia. After adding 150-oleic acid to the precipitate and heating at 100° C. for 5 minutes, water was added and the mixture was quenched.
次いで］、ＮＨＣｌ２を撹拌しながら加え、凝集させた
後、凝集体を？濾過弁離し、水分を除去した後、トルエ
ンＩＯ−を加えてコロイド状のマグネタイトを得た。Then], NHCl2 was added with stirring to cause agglomeration, and then the agglomerates were ? After releasing the filtration valve and removing water, toluene IO- was added to obtain colloidal magnetite.
（３）前記コロイド状のマグネタイトｌ−にγ−アミノ
プロピルトリエトキシシラン０．３−およびトルエン０
．２−を混合し、室温で５０分間反応させ、沈澱を生成
させた後、エタノールと水で洗浄し水中に保存した。(3) The colloidal magnetite l- is added with 0.3-aminopropyltriethoxysilane and 0.3-gamma-aminopropyltriethoxysilane and 0.
．． 2- were mixed and reacted at room temperature for 50 minutes to form a precipitate, which was then washed with ethanol and water and stored in water.
（４）前記γ−アミノプロピルトリエトキシシランを導
入したコロイド状のマグネタイトとグルタルアルデヒド
を混合、反応させ、コロイド状のマグネタイトにホルミ
ル基を導入した。(4) Colloidal magnetite into which the γ-aminopropyltriethoxysilane was introduced was mixed and reacted with glutaraldehyde to introduce a formyl group into the colloidal magnetite.
（５）前記（４）の処理を施したコロイド状のマグネタ
イトと肺癌の癌細胞と特異的に結合するモノクロナール
抗体とをりん酸生理食塩水中で混合して反応させた後、
水素化ホウ素ナトリウムで還元処理して、抗体を固定し
た。(5) After mixing the colloidal magnetite treated in (4) above and a monoclonal antibody that specifically binds to lung cancer cells in phosphate saline and reacting,
Antibodies were immobilized by reduction treatment with sodium borohydride.
前記抗体が結合したマグネタイトを癌細胞と混合したと
ころ、極めて効率的に癌細胞付近に集中し、さらに、１
ＯＫＨｚの高周波磁場中においたところ、マグネタイト
が発熱し癌細胞のみが選択的に死滅したことが確認され
た。When the magnetite bound to the antibody was mixed with cancer cells, it concentrated very efficiently near the cancer cells, and furthermore, 1
When placed in a high frequency magnetic field of OKHz, it was confirmed that magnetite generated heat and only cancer cells were selectively killed.
実施例２
本実施例は、基本的には、実施例１と同様であるが、前
記（３）、（４）の工程においてγ−アミノプロピルト
リエトキシシランに代えてビニルトリメトキシシランを
使用し、クルクルアルデヒドに代えてアクリルアルデヒ
ドを使用して反応させ、抗体が結合したマグネタイトを
得た。Example 2 This example is basically the same as Example 1, except that vinyltrimethoxysilane was used instead of γ-aminopropyltriethoxysilane in steps (3) and (4). The reaction was carried out using acrylaldehyde instead of curcuraldehyde to obtain antibody-bound magnetite.
この抗体が結合したマグネタイトも、実施例１で得た抗
体を結合したマグネタイトと同様に極めて効率的に癌細
胞付近に集中し、さらに１０ＫＨｚの高周波磁場中にお
いたところ、マグネタイトが発熱し癌細胞のみが選択的
に死滅したことが確認された。Similar to the antibody-bound magnetite obtained in Example 1, this antibody-bound magnetite concentrates very efficiently near cancer cells, and when placed in a 10 KHz high-frequency magnetic field, the magnetite generates heat and concentrates only in cancer cells. It was confirmed that the cells were selectively killed.
実施例３
（１）パーマロイΔ級（Ｎｉ７８．５％、Ｆｅ２１．５
％）の微粉末（直径Ｑ、ｌｐｍ）の表面を加熱酸化した
。Example 3 (1) Permalloy Δ class (Ni78.5%, Fe21.5
%) fine powder (diameter Q, lpm) was heated and oxidized.
（２）パーマロイ微粉末をトルエンに分散させた溶液１
−に、γ−アミノプロピルトリエトキシシラン０．３−
およびトルエン０． ２１ｎＩ！を混合し、室温で５０
分間反応させた後、エタノールと水で洗浄し、水中に保
存した。(2) Solution 1 of permalloy fine powder dispersed in toluene
-, γ-aminopropyltriethoxysilane 0.3-
and toluene 0. 21nI! Mix and leave at room temperature for 50
After reacting for a minute, it was washed with ethanol and water and stored in water.
（３）ついで、クルクルアルデヒドと混合、反応させ、
ホルミル基を導入した。(3) Then, mixed with curcuraldehyde and reacted,
A formyl group was introduced.
（４）ホルミル基が導入されたパーマロイと肺癌の癌細
胞と特異的に結合するモノクロナール抗体とをりん酸生
理食塩水中で混合して反応させた後、水素化ホウ素ナト
リウムで還元処理して、抗体を固定した。(4) Permalloy into which a formyl group has been introduced and a monoclonal antibody that specifically binds to cancer cells of lung cancer are mixed and reacted in phosphate saline, and then subjected to reduction treatment with sodium borohydride, Antibodies were immobilized.
前記抗体が結合したパーマロイを癌細胞と混合したとこ
ろ、極めて効率的に癌細胞付近に集中し、さらに、１０
ｋＨｚの高周波磁場中においたところ、パーマロイが発
熱し、癌細胞のみが選択的に死滅したことが確認された
。When permalloy to which the above antibody was bound was mixed with cancer cells, it concentrated extremely efficiently near the cancer cells, and furthermore, 10
When placed in a kHz high-frequency magnetic field, Permalloy generated heat, and it was confirmed that only cancer cells were selectively killed.
［発明の効果１
上述の如く、本発明の抗体が結合した磁性微粒子は、電
磁波を吸収して発熱する磁性微粒子の表面に癌細胞に選
択的に結合する抗体が結合したちのであって、癌細胞の
付近に選択的に集中させることができ、しかも磁性微粒
子自体が発熱するため、癌細胞以外を過熱することなく
温熱療法を行うことができるものである。[Effect of the invention 1 As described above, the magnetic fine particles to which the antibodies of the present invention are bound have antibodies that selectively bind to cancer cells bound to the surface of the magnetic fine particles that absorb electromagnetic waves and generate heat. Since they can be selectively concentrated near cells and the magnetic particles themselves generate heat, thermotherapy can be performed without overheating anything other than cancer cells.
Claims (1)
細胞に選択的に結合する抗体が結合した磁性微粒子。 ２、前記電磁波が、高周波磁場である請求項１記載の磁
性微粒子。 ３、前記電磁波の周波数が、１ＫＨｚ−１ ＭＨｚの高周波磁場である請求項２記載の磁性微粒子。 ４、前記磁性微粒子が、強磁性微粒子である請求項１記
載の磁性微粒子。 ５、前記磁性微粒子の粒径が５μｍ以下である請求項１
記載の磁性微粒子。 ６、磁性微粒子に二官能性架橋剤を結合させた後、これ
に癌細胞に選択的に結合する抗体を反応させることを特
徴とする抗体が結合した磁性微粒子の製造方法。[Scope of Claims] 1. Magnetic fine particles that generate heat by absorbing electromagnetic waves, and have an antibody that selectively binds to cancer cells bound to the surface of the magnetic fine particles. 2. The magnetic fine particles according to claim 1, wherein the electromagnetic wave is a high frequency magnetic field. 3. The magnetic fine particles according to claim 2, wherein the frequency of the electromagnetic wave is a high frequency magnetic field of 1 KHz-1 MHz. 4. The magnetic fine particles according to claim 1, wherein the magnetic fine particles are ferromagnetic fine particles. 5. Claim 1, wherein the magnetic fine particles have a particle size of 5 μm or less.
The magnetic fine particles described. 6. A method for producing antibody-bound magnetic fine particles, which comprises binding a bifunctional cross-linking agent to magnetic fine particles and then reacting the magnetic fine particles with an antibody that selectively binds to cancer cells.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16976289 | 1989-07-03 | ||
| JP1-169762 | 1989-07-03 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH03128331A true JPH03128331A (en) | 1991-05-31 |
| JP3102007B2 JP3102007B2 (en) | 2000-10-23 |
Family
ID=15892382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP01316576A Expired - Lifetime JP3102007B2 (en) | 1989-07-03 | 1989-12-07 | Antibody-bound magnetic microparticles used for tumor hyperthermia |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3102007B2 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004067015A1 (en) * | 2003-01-31 | 2004-08-12 | Otsuka Pharmaceutical Factory, Inc. | Auxiliary agent to be used in cancer therapy by dielectric heating and cancer therapy method |
| JP2007536016A (en) * | 2004-05-07 | 2007-12-13 | サーム メッド エルエルシー | Enhanced system and method for RF guided hyperthermia |
| JP2008019202A (en) * | 2006-07-12 | 2008-01-31 | Koichi Jinbo | Melanoma targeted hyperthermia therapy |
| WO2010026638A1 (en) * | 2008-09-04 | 2010-03-11 | 株式会社ナノセラピー研究所 | Hyperthermic therapy kit for malignant tumor comprising anti-regulatory-t-cell antibody and magnetic microparticle, and hyperthermic therapy using the kit |
| WO2011062217A1 (en) | 2009-11-20 | 2011-05-26 | 戸田工業株式会社 | Magnetic iron oxide microparticle powder, aqueous dispersion containing magnetic particles, and process for production of same |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6037368B1 (en) * | 2016-06-20 | 2016-12-07 | 株式会社ジャスト | Product tag |
| US12128245B2 (en) * | 2018-04-13 | 2024-10-29 | Kwangwoon University Industry-Academic Collaboration Foundation | RF microchip for induction of cancer cells migration for radio frequency thermal therapy for cancer treatment or removal surgery |
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| US4323056A (en) * | 1980-05-19 | 1982-04-06 | Corning Glass Works | Radio frequency induced hyperthermia for tumor therapy |
| JPS60169765A (en) * | 1984-02-14 | 1985-09-03 | Sugiura Shinyaku Kaihatsu Kenkyusho:Kk | Reagent for measuring placental alkaline phosphatase |
| DE3502998A1 (en) * | 1985-01-30 | 1986-07-31 | Detlef Dr. 5100 Aachen Müller-Schulte | Compositions for selective tumour therapy and processes for the preparation and use thereof |
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|---|---|---|---|---|
| US4323056A (en) * | 1980-05-19 | 1982-04-06 | Corning Glass Works | Radio frequency induced hyperthermia for tumor therapy |
| JPS60169765A (en) * | 1984-02-14 | 1985-09-03 | Sugiura Shinyaku Kaihatsu Kenkyusho:Kk | Reagent for measuring placental alkaline phosphatase |
| DE3502998A1 (en) * | 1985-01-30 | 1986-07-31 | Detlef Dr. 5100 Aachen Müller-Schulte | Compositions for selective tumour therapy and processes for the preparation and use thereof |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004067015A1 (en) * | 2003-01-31 | 2004-08-12 | Otsuka Pharmaceutical Factory, Inc. | Auxiliary agent to be used in cancer therapy by dielectric heating and cancer therapy method |
| CN1744906B (en) * | 2003-01-31 | 2010-08-18 | 株式会社大塚制药工厂 | Adjuvant used in cancer treatment method using dielectric heating and cancer treatment method |
| US9056128B2 (en) | 2003-01-31 | 2015-06-16 | Otsuka Pharmaceutical Factory, Inc. | Adjuvant used in dielectric heating-assisted cancer treatment, and cancer treatment method |
| JP2007536016A (en) * | 2004-05-07 | 2007-12-13 | サーム メッド エルエルシー | Enhanced system and method for RF guided hyperthermia |
| JP2008019202A (en) * | 2006-07-12 | 2008-01-31 | Koichi Jinbo | Melanoma targeted hyperthermia therapy |
| WO2010026638A1 (en) * | 2008-09-04 | 2010-03-11 | 株式会社ナノセラピー研究所 | Hyperthermic therapy kit for malignant tumor comprising anti-regulatory-t-cell antibody and magnetic microparticle, and hyperthermic therapy using the kit |
| JP5529023B2 (en) * | 2008-09-04 | 2014-06-25 | 猛 小林 | Kit for hyperthermia treatment of malignant tumor containing anti-regulatory T cell antibody and magnetic fine particles |
| AU2008361497B2 (en) * | 2008-09-04 | 2014-07-17 | Takeshi Kobayashi | Methods and kits for hyperthermia and CTLA4 inhibitory therapy |
| WO2011062217A1 (en) | 2009-11-20 | 2011-05-26 | 戸田工業株式会社 | Magnetic iron oxide microparticle powder, aqueous dispersion containing magnetic particles, and process for production of same |
| US9127168B2 (en) | 2009-11-20 | 2015-09-08 | Toda Kogyo Corporation | Magnetic iron oxide fine particles, and magnetic particle-containing water dispersion and process for producing the same |
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