JP4964217B2 - ヒト免疫療法 - Google Patents
ヒト免疫療法 Download PDFInfo
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- JP4964217B2 JP4964217B2 JP2008306469A JP2008306469A JP4964217B2 JP 4964217 B2 JP4964217 B2 JP 4964217B2 JP 2008306469 A JP2008306469 A JP 2008306469A JP 2008306469 A JP2008306469 A JP 2008306469A JP 4964217 B2 JP4964217 B2 JP 4964217B2
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Description
[1] 癌および/または微生物感染症に罹患した患者のリンパ節において癌細胞または微生物を排除することを特徴とする、癌および/または微生物感染症を処置または予防するための、細菌菌体成分を有効成分として含有する医薬組成物、
に関するものである。
本発明者は、細菌菌体成分を用いた免疫療法による上記治療の過程において、患者に出現するリンパ節の腫脹に、主に以下のような3通りの類型があることを見出した。
BCG-CWSは、文献記載の方法(Azumaら、J. Natl. Cancer. Inst. 52: 95-101(1974) )に従って調製できる。
BCG-CWSは、常に単独接種が原則である。
癌患者リンパ節の一部を外科手術においてサンプリングし、種々の免疫マーカーについて調べた。その結果を臨床所見とともにまとめた。
(1)症例1:60才、女性、
病名:卵巣癌(明細胞癌)、ステージIa(T1aNxMx)
病名:乳癌(乳頭腺管癌)、ステージII(T2aN1bM0)。
病名:子宮頸癌(小細胞癌)、臨床的にはステージIb(T1bNxM0)
病名:乳癌(浸潤性乳管癌、2a3硬癌)、ステージIIIa(T3NxM0)。
現在まで、約30年間、BCG-CWS単独免疫療法を実施してきた結果、癌患者においては、一般的に免疫力が低下しているため、健康な人以上に感染症に罹患する可能性が高いにもかかわらず、感染症の発症例が著しく少ないことを見いだした。
(1)症例1(56才、女性)
病名:上顎癌(扁平上皮癌)、ステージIII(T3bN0M0))。
病名:肺癌(腺癌)、ステージIb(T2N0M0))
癌の免疫療法剤として、微生物死菌、細菌の細胞壁骨格成分、ムラミルジペプチド(MDP)、リポ多糖(LPS)等の細菌菌体成分等からなる、BRM(biological response modifier, 生体反応修飾物質)と呼ばれる一連の物質がある。これらのうち、細菌の細胞壁骨格成分は、例えば実験的腫瘍系およびヒト癌の免疫療法において抗腫瘍活性を示すこと等が知られている。(Cancer Res., 33, 2187-2195(1973)、J. Nat. Cancer Inst., 48, 831-835(1972)、J. Bacteriol., 94, 1736-1745(1967)、Gann, 69, 619-626(1978)、J. Bacteriol., 92, 869-879(1966))。菌体成分としては、例えば生菌そのものであるBCG(Bacille Calmette-Guerin)菌を用いた癌免疫療法剤に関して、今まで多くの治療成績が蓄積されている。
Claims (2)
- BCG−CWSを有効成分として含有する、メチシリン耐性黄色ブドウ球菌感染症を予防または治療するための医薬組成物。
- 癌に罹患した患者の、担癌組織を切除する外科手術後のメチシリン耐性黄色ブドウ球菌感染症を予防または治療するためのものである、請求項1記載の医薬組成物。
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JP2008306469A JP4964217B2 (ja) | 2001-07-19 | 2008-12-01 | ヒト免疫療法 |
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JP2008306469A Expired - Fee Related JP4964217B2 (ja) | 2001-07-19 | 2008-12-01 | ヒト免疫療法 |
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EP (1) | EP1415655A4 (ja) |
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Families Citing this family (13)
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CN1230184C (zh) | 1998-07-16 | 2005-12-07 | 东市郎 | 以细菌的菌体成分为有效成分的癌免疫治疗用制剂 |
US9107864B2 (en) | 2004-06-07 | 2015-08-18 | Qu Biologics Inc. | Tissue targeted antigenic activation of the immune response to treat cancers |
US8501198B2 (en) | 2004-06-07 | 2013-08-06 | Qu Biologics Inc. | Tissue targeted antigenic activation of the immune response to treat cancers |
US8034359B2 (en) | 2004-06-07 | 2011-10-11 | Qu Biologics Inc. | Tissue targeted antigenic activation of the immune response to cancers |
AU2005251397B2 (en) * | 2004-06-07 | 2010-11-11 | Qu Biologics Inc. | Bacterial compositions for the treatment of cancer |
CN1935262B (zh) * | 2005-09-23 | 2010-12-29 | 沈阳胜宝康生物制药有限公司 | 红色诺卡氏菌细胞壁骨架在制备抗人乳头瘤病毒药物的用途 |
CN101073583A (zh) * | 2006-05-19 | 2007-11-21 | 沈阳胜宝康生物制药有限公司 | 红色诺卡氏菌细胞壁骨架在制备药物中的用途 |
BRPI0722054A2 (pt) * | 2006-12-28 | 2014-04-01 | Limerick Biopharma Inc | Composição, kit, e métodos para diminuir um efeito colateral de tratamento com um inibidor da calcineurina, para aumentar um efeito terapêutico de um inibidor da calcineurina e para mudar a concentração de tacrolimus ou um análogo de tacrolimus em um compartimento fisiológico. |
US8980279B2 (en) | 2010-07-26 | 2015-03-17 | Qu Biologics | Personalized site-specific immunomodulation |
NZ702796A (en) | 2010-07-26 | 2017-03-31 | Qu Biologics Inc | Immunogenic anti-inflammatory compositions |
CN102526119A (zh) * | 2010-12-23 | 2012-07-04 | 辽宁纳可佳生物制药有限公司 | 红色诺卡氏菌细胞壁骨架增强树突状细胞功能的方法 |
JP6074676B2 (ja) * | 2011-08-19 | 2017-02-08 | 公立大学法人横浜市立大学 | 組織因子経路阻害因子2(tfpi2)測定による卵巣明細胞腺癌の検査方法および検査薬 |
CA2947631A1 (en) | 2014-05-02 | 2015-11-05 | Qu Biologics Inc. | Anti-microbial immunomodulation |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
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JPS54140710A (en) * | 1978-03-10 | 1979-11-01 | Mitsui Toatsu Chem Inc | Anti-tumor substance and its preparation |
US4503048A (en) | 1982-06-30 | 1985-03-05 | Ribi Immunochem Research, Inc. | Pyridine soluble extract of a microorganism |
JPS5995220A (ja) | 1982-11-22 | 1984-06-01 | Ajinomoto Co Inc | 免疫療法剤 |
JPS59161320A (ja) | 1983-03-04 | 1984-09-12 | Maruyama Chisato | リポ多糖体およびその製造法 |
US4744984A (en) | 1985-10-08 | 1988-05-17 | Vetrepharm Research, Inc. | Antiviral immunotherapeutic agent and preparation thereof |
NZ219027A (en) * | 1986-01-24 | 1989-09-27 | Genentech Inc | Antiviral composition containing interferon tumour necrosis factor and/or lymphotoxin |
JPS6448154A (en) * | 1987-08-19 | 1989-02-22 | Fujitsu Ltd | Bus arbitrating circuit with timeout monitor |
US6284255B1 (en) * | 1996-08-29 | 2001-09-04 | Genesis Research & Development Corporation Limited | Compounds and methods for treatment and diagnosis of mycobacterial infections |
JPH10306029A (ja) * | 1997-03-07 | 1998-11-17 | Akira Hayashi | 細菌の菌体成分を有効成分とする癌免疫療法剤 |
US6593096B1 (en) | 1997-03-07 | 2003-07-15 | Akira Hayashi | Immunotherapeutic agent for cancer containing nucleoidal component of bacterium as active ingredient |
JP2001519785A (ja) | 1997-04-02 | 2001-10-23 | バイオニケ ライフ サイエンシーズ インコーポレイテッド | 局所的障害および創傷の治療のための細菌細胞壁抽出物の使用 |
US6849452B1 (en) * | 1998-03-03 | 2005-02-01 | Institut Gustave Roussy | Methods for activating natural killer (NK) cells and means for carrying out said methods |
DK1077711T3 (da) | 1998-04-29 | 2005-05-23 | Medac Klinische Spezialpraep | Behandling af papillomavirusinfektion under anvendelse af en mycobakterie |
CN1230184C (zh) | 1998-07-16 | 2005-12-07 | 东市郎 | 以细菌的菌体成分为有效成分的癌免疫治疗用制剂 |
WO2001048154A1 (fr) | 1999-12-28 | 2001-07-05 | Toyoshima, Kumao | Agent de maturation pour cellules dendritiques immatures |
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- 2002-07-19 EP EP02751649A patent/EP1415655A4/en not_active Withdrawn
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JPWO2003009859A1 (ja) | 2004-11-11 |
US7273602B2 (en) | 2007-09-25 |
JP2009102332A (ja) | 2009-05-14 |
EP1415655A1 (en) | 2004-05-06 |
US20070172499A1 (en) | 2007-07-26 |
US20040208896A1 (en) | 2004-10-21 |
US7521040B2 (en) | 2009-04-21 |
WO2003009859A1 (fr) | 2003-02-06 |
EP1415655A4 (en) | 2005-12-21 |
JP4859341B2 (ja) | 2012-01-25 |
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