JP2014513126A - 免疫療法を用いたil−12の誘導 - Google Patents
免疫療法を用いたil−12の誘導 Download PDFInfo
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- JP2014513126A JP2014513126A JP2014509386A JP2014509386A JP2014513126A JP 2014513126 A JP2014513126 A JP 2014513126A JP 2014509386 A JP2014509386 A JP 2014509386A JP 2014509386 A JP2014509386 A JP 2014509386A JP 2014513126 A JP2014513126 A JP 2014513126A
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Abstract
Description
本発明は、免疫細胞を用いた治療法に関する。より具体的には、本発明は、患者におけるIL−12の産生を促進する免疫細胞療法に関する。
[背景]
既知の最も的確、かつ強力で安全な疾病の予防および治療のメカニズムは、先天性免疫および適応免疫の双方の要素を組み合わせて、医学的な介入を行わずに多種多様な外来病原体を除去する、自然「滅菌」免疫応答である。免疫系は、再感染時に迅速に免疫応答を開始するために、除去された外来抗原を「記憶する」ように構築されている。免疫系は、癌患者の免疫系でさえも、ウイルスやバクテリアでみられるような外来抗原を認識することができ、また、該外来抗原を完全に破壊して身体から除去するのに十分な、外来抗原に対する応答を開始することができる。この滅菌免疫応答の強烈性および特異性を確認することができるのは、不全に陥り低下した免疫系によって、自己組織は影響されないながらも、例えば腎臓、肝臓、または心臓などのような大きな移植臓器が完全に破壊され得ることにおいて、確認することができる。外来抗原に対するこのような免疫の破壊効果は、患者の免疫応答が低下しているが故に逃避した腫瘍および/または他の抗原に転換し得ると、有益となるだろう。
本発明は、患者の血漿中のIL−12を検出可能なレベルに導く組成物および方法に関する。本発明は、患者に投与された場合に、重篤な毒性を生じることなく、患者の血漿中の内因性IL−12を検出可能なレベルで産生し得るように導く組成物を含む。内因性IL−12は、驚くことに、癌患者において検出され得る。該組成物は、好ましくは、同種異系活性化T細胞を含む。T細胞は、IL−12を産生することができないため、患者に投与されたT細胞組成物は、患者自身のAPCによるIL−12の産生を引き起こす。
本発明は、患者の疾病を治療する方法も含む。その疾病には、病原体によって引き起こされた疾病だけでなく、上述のような癌性腫瘍や血液悪性疾患が含まれ得る。患者におけるTh1応答の影響を受けやすい他の疾病もまた、本明細書に記載された方法を用いて治療することが可能である。患者は、本明細書に記載された方法に従って、同種異系組成物を投与される。そして、患者の血漿は、IL−12が存在するかについて監視される。内因性IL−12の検出は、その疾病に対する患者の免疫応答を示唆するものとなり得る。IL−12のレベルを維持するために治療用組成物を追加で投与し、それによって、当該疾病抗原に対する患者の免疫応答を維持してもよい。
[例]
本研究は、同種異系活性化Th1細胞で治療された患者の血漿中におけるIL−12のレベルを監視するために行われた。活性化同種異系Th1細胞およびその調製方法は、米国特許第7,435,592号に記載されている。活性化同種異系Th1細胞は、意図的に患者に不適合であった。皮内注射−活性化同種異系Th1細胞が皮内注射によって投与された。該細胞は、1mlに1×107個/mlの密度で懸濁された。
冷凍アブレーションは、CryoCare−28経皮的プローブシステム(米国カリフォルニア州のエンドケア)を使用して行われた。このシステムは、ジュール−トムソン効果を使用して、閉鎖系中で冷凍器の先端部を冷却した。ガス係数とノズルの寸法とに応じて、異なる気体要素は、当該ノズルに近接する領域にて異なる熱交換現象を生じる。アルゴンガスが冷却(−187℃)に用いられ、ヘリウムが加熱(67℃)に用いられた。
表1、2、および3は、記載された日数における、具体的な治療のタイミングと患者の血漿中のIL−12のレベルとを示す。図1は、本研究中の患者の免疫系によるIL−12の発現を図示するグラフである。
Claims (30)
- 血漿中にIL−12の発現を引き起こすことが可能な組成物であって、
該組成物は、
外来抗原と、
少なくとも1つのTh1サイトカインと、
DC成熟分子と
を本質的に含む、組成物。 - 請求項1に記載の組成物であって、
前記外来抗原は、同種抗原である、組成物。 - 請求項1に記載の組成物であって、
前記Th1サイトカインは、IL−1、IL−2、IL−6、IL−8、IL−15、インターフェロン−ガンマ、TNF−アルファ、GM−CSFのうちの、1つ以上である、組成物。 - 請求項1に記載の組成物であって、
前記DC成熟分子は、CD40Lおよび/またはFasLである、組成物。 - 請求項2に記載の組成物であって、
前記同種抗原は、生きているT細胞上にある、組成物。 - 請求項5に記載の組成物であって、
前記T細胞は、CD4+細胞またはTh1細胞である、組成物。 - 請求項6に記載の組成物であって、
前記Th1細胞は、活性化される、組成物。 - 請求項7に記載の組成物であって、
前記Th1細胞は、CD3とCD28とが架橋結合されることによって活性化される、組成物。 - 請求項8に記載の組成物であって、
前記活性化されたTh1細胞は、IL−2、IFN−ガンマ、およびGM−CSFであるTh1サイトカインのうちの1つ以上を分泌する、組成物。 - 請求項9に記載の組成物であって、
前記活性化されたTh1細胞は、該細胞の表面上にて、前記DC成熟分子であるCD40Lおよび/またはFasLを発現する、組成物。 - 請求項1に記載の組成物であって、
前記成分は、表面に固定される、組成物。 - 請求項11に記載の組成物であって、
前記表面は、生分解性を有する、組成物。 - 請求項5に記載の組成物であって、
前記生きているT細胞は、注入器または可撓性容器に詰められる、組成物。 - 請求項13に記載の組成物であって、
前記細胞は、1x107個/ml以上の濃度である、組成物。 - 請求項14に記載の組成物であって、
前記細胞は、非栄養培地に懸濁される、組成物。 - 患者におけるIL−12の血漿中レベルを増加する方法であって、
同種異系細胞の少なくとも一部が活性化T細胞である、該同種異系細胞を含む組成物を投与することと、
前記患者の前記IL−12のレベルを監視することと、
前記患者の前記血漿中にIL−12が十分なレベルで検出されない場合に、前記組成物を再投与することと
を備える、方法。 - 請求項16に記載の方法であって、
前記IL−12の検出は、前記患者に対して毒性がない、方法。 - 請求項16に記載の方法であって、
前記活性化T細胞は、CD4+細胞である、方法。 - 請求項18に記載の方法であって、
前記活性化CD4細胞は、Th1細胞である、方法。 - 請求項19に記載の方法であって、
前記Th1細胞は、CD3とCD28とが架橋結合されることによって活性化される、方法。 - 請求項16に記載の方法であって、
前記組成物の投与によって、前記患者における前記IFN−ガンマのレベル、および/または、前記Th1応答が増加される、方法。 - 請求項16に記載の方法であって、
前記患者の前記血漿中の前記IL−12のレベルは、少なくとも約5000pg/mlである、方法。 - 疾病を有する患者を治療する方法であって、
同種異系細胞を含む組成物を投与することであって、少なくとも一部が活性化T細胞であり、該T細胞上にて該細胞表面部分に結合された1つ以上の因子を架橋結合することによって当該T細胞が活性化される、同種異系細胞を含む組成物を投与することと、
前記患者の血漿中のIL−12のレベルを監視することと、
前記患者の前記血漿中においてIL−12が検出されない場合に、前記組成物を再投与することと、
を備える、方法。 - 請求項23に記載の方法であって、
前記疾病は、癌であるか、または、病原性感染の結果である、方法。 - 請求項23に記載の方法であって、
前記内因性IL−12の前記濃度が検出可能となるまで前記再投与が繰り返される、方法。 - 内因性IL−12のレベルを増加させるための治療用組成物であって、
活性化同種異系T細胞を備え、前記組成物の投与によって、患者に毒性を与えることなく内因性IL−12のレベルが該患者の血漿中で検出可能になる、組成物。 - 請求項26に記載の組成物であって、
前記患者は、癌または感染症を有する、組成物。 - 請求項26に記載の組成物であって、
前記T細胞は、CD4+細胞である、組成物。 - 請求項26に記載の組成物であって、
前記T細胞上にて細胞表面部分に結合された1つ以上の因子を架橋結合することによって当該T細胞が活性化される、組成物。 - 請求項26に記載の組成物であって、
前記1つ以上の因子は、抗CD3および抗CD28モノクローナル抗体などの、モノクローナル抗体である、組成物。
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US61/528,484 | 2011-08-29 | ||
US201161564551P | 2011-11-29 | 2011-11-29 | |
US61/564,551 | 2011-11-29 | ||
US201261582881P | 2012-01-04 | 2012-01-04 | |
US61/582,881 | 2012-01-04 | ||
PCT/US2012/036123 WO2012151279A2 (en) | 2011-05-03 | 2012-05-02 | Induction of il-12 using immunotherapy |
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CN105792883B (zh) | 2013-12-05 | 2019-11-05 | 飞慕控股有限责任公司 | 利用射频电学膜击穿(rf-emb)的癌症免疫疗法 |
JP6202339B2 (ja) * | 2013-12-19 | 2017-09-27 | 国立研究開発法人国立精神・神経医療研究センター | GM−CSF産生T細胞制御剤、及びTh1/Th2免疫バランス調節剤 |
WO2016123608A2 (en) | 2015-01-30 | 2016-08-04 | Rfemb Holdings, Llc | Radio-frequency electrical membrane breakdown for the treatment of high risk and recurrent prostate cancer, unresectable pancreatic cancer, tumors of the breast, melanoma or other skin malignancies, sarcoma, soft tissue tumors, ductal carcinoma, neoplasia, and intra and extra luminal abnormal tissue |
TWI834598B (zh) | 2016-01-15 | 2024-03-11 | 美商Rfemb控股有限公司 | 癌症之免疫治療 |
CN115337323A (zh) * | 2017-07-14 | 2022-11-15 | 徐民桢 | 用于诱导m1优势免疫应答的方法和药物组合物 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007500217A (ja) * | 2003-05-13 | 2007-01-11 | マイケル ハル−ノイ, | 同種異系細胞治療:ミラー効果 |
JP2007526314A (ja) * | 2004-03-01 | 2007-09-13 | イミュノバティブ セラピーズ, リミテッド | 細胞治療処方方法および組成物 |
WO2009135199A2 (en) * | 2008-05-02 | 2009-11-05 | Immunovative Therapies, Ltd. | Vaccine compositions and methods |
JP2010509337A (ja) * | 2006-11-13 | 2010-03-25 | イミュノバティブ セラピーズ, リミテッド | 切除的免疫療法 |
JP2010536330A (ja) * | 2007-08-16 | 2010-12-02 | セル メト リサーチ ゲゼルシャフト ミット ベシュレンクテル ハフツング | 樹状細胞 |
Family Cites Families (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2439003A1 (fr) | 1978-10-20 | 1980-05-16 | Anvar | Nouvelles pieces d'osteosynthese, leur preparation et leur application |
US5766920A (en) | 1982-08-11 | 1998-06-16 | Cellcor, Inc. | Ex vivo activation of immune cells |
AU7873187A (en) | 1986-08-08 | 1988-02-24 | University Of Minnesota | Method of culturing leukocytes |
PT89121A (pt) | 1987-12-04 | 1989-12-29 | Du Pont | Processo para a preparacao de interleuquina-2 imobilizada e interleuquina-2 contendo uma extensao no terminal-carboxilo com actividade de interleuquina-2 natural |
US6352694B1 (en) | 1994-06-03 | 2002-03-05 | Genetics Institute, Inc. | Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells |
US6534055B1 (en) | 1988-11-23 | 2003-03-18 | Genetics Institute, Inc. | Methods for selectively stimulating proliferation of T cells |
US6905680B2 (en) | 1988-11-23 | 2005-06-14 | Genetics Institute, Inc. | Methods of treating HIV infected subjects |
US5126132A (en) | 1989-08-21 | 1992-06-30 | The United States Of America As Represented By The Department Of Health And Human Services | Tumor infiltrating lymphocytes as a treatment modality for human cancer |
US5728388A (en) | 1989-10-03 | 1998-03-17 | Terman; David S. | Method of cancer treatment |
JPH0455577A (ja) | 1990-06-22 | 1992-02-24 | Mitsubishi Electric Corp | 構造物の制振装置 |
AU5729294A (en) | 1992-11-25 | 1994-06-22 | Tanox Biosystems, Inc. | Conjugates and constructs including anti-cd28 and anti-cd3 binding molecules |
DE69430315T2 (de) | 1993-08-06 | 2002-11-21 | Epimmune Inc | Methoden zur (ex vivo) therapie mittels peptid - bestueckten antigen - praesentierenden zellen zur aktivierung von ctl |
IL107483A0 (en) | 1993-11-03 | 1994-02-27 | Yeda Res & Dev | Bone marrow transplantation |
US5827642A (en) | 1994-08-31 | 1998-10-27 | Fred Hutchinson Cancer Research Center | Rapid expansion method ("REM") for in vitro propagation of T lymphocytes |
US6461867B1 (en) | 1995-03-08 | 2002-10-08 | The Scripps Research Institute | Synthetic antigen presenting matrix |
DE19545257A1 (de) | 1995-11-24 | 1997-06-19 | Schering Ag | Verfahren zur Herstellung von morphologisch einheitlichen Mikrokapseln sowie nach diesem Verfahren hergestellte Mikrokapseln |
JPH09255577A (ja) * | 1996-03-27 | 1997-09-30 | Dainippon Ink & Chem Inc | インターリュウキン−12誘導剤 |
EP0969865B1 (en) | 1996-05-23 | 2006-12-06 | The Scripps Research Institute | Mhc class ii antigen-presenting systems and methods for activating cd4?+ t cells |
AU5596898A (en) | 1996-12-03 | 1998-06-29 | Osteobiologics, Inc. | Biodegradable polymeric film |
CA2278847A1 (en) | 1997-01-31 | 1998-08-06 | Hemosol Inc. | Method for the production of selected lymphocytes |
EP1014897B1 (en) | 1997-05-30 | 2008-10-29 | Osteobiologics, Inc. | Fiber-reinforced, porous, biodegradable implant device |
CA2309206A1 (en) | 1997-11-10 | 1999-05-20 | Arch Development Corporation | Methods for treatment of tumors and tumor cells using ex vivo activated t cells |
AU4518400A (en) | 1999-07-12 | 2001-01-18 | Isotis B.V. | Sutures |
ATE373078T1 (de) | 2000-02-24 | 2007-09-15 | Xcyte Therapies Inc | Gleichzeitige stimulation und konzentration von zellen |
US6867041B2 (en) | 2000-02-24 | 2005-03-15 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
US20030119185A1 (en) | 2000-02-24 | 2003-06-26 | Xcyte Therapies, Inc. | Activation and expansion of cells |
WO2001062092A1 (en) | 2000-02-25 | 2001-08-30 | Thomas Jefferson University | Formulations and methods for using the same to elicit an immune response |
AU2001292564A1 (en) | 2000-08-31 | 2002-03-13 | Emory University | A method of transplantation using chemotherapy-treated allogeneic cells that enhance immune responses without graft versus host disease |
US6626950B2 (en) | 2001-06-28 | 2003-09-30 | Ethicon, Inc. | Composite scaffold with post anchor for the repair and regeneration of tissue |
US20040258661A1 (en) | 2001-10-31 | 2004-12-23 | Daniel Fowler | Generation of use of tc1 and tc2 cells |
US20030134415A1 (en) * | 2001-09-19 | 2003-07-17 | Gruenberg Micheal L. | Th1 cell adoptive immunotherapy |
US7105580B2 (en) | 2001-12-06 | 2006-09-12 | University Of Washington | Porous structures useful for growing living tissue, and methods of manufacture |
US20030175272A1 (en) | 2002-03-07 | 2003-09-18 | Medcell Biologics, Inc. | Re-activated T-cells for adoptive immunotherapy |
DE10230223A1 (de) | 2002-07-04 | 2004-01-22 | Tegenero Ag | Mikropartikel mit CD28-spezifischen monoklonalen Antikörpern |
CN1399054A (zh) * | 2002-09-03 | 2003-02-26 | 宋有财 | 旋转式的泊车装置 |
US20110142887A1 (en) | 2009-12-15 | 2011-06-16 | Immunovative Therapies Ltd. | Methods and compositions for liquidation of tumors |
US7402431B2 (en) | 2004-03-01 | 2008-07-22 | Immunovative Therapies, Ltd. | T-cell therapy formulation |
US7371228B2 (en) | 2003-09-19 | 2008-05-13 | Medtronic Vascular, Inc. | Delivery of therapeutics to treat aneurysms |
US7592431B2 (en) | 2004-02-26 | 2009-09-22 | Immunovative Therapies, Ltd. | Biodegradable T-cell Activation device |
LT2573166T (lt) | 2004-02-26 | 2016-09-26 | Immunovative Therapies, Ltd. | T ląstelių paruošimo būdas ląstelių terapijai |
US7446099B2 (en) | 2004-02-27 | 2008-11-04 | Nitto Denko Corporation | Compositions and methods for biodegradable polymer-peptide mediated transfection |
CA2557436A1 (en) | 2004-03-05 | 2005-09-29 | The Trustees Of Columbia University In The City Of New York | Polymer-ceramic-hydrogel composite scaffold for osteochondral repair |
US8865224B2 (en) | 2004-10-14 | 2014-10-21 | Immunovative Therapies Ltd. | Allogeneic cellular immunotherapy for opportunistic infection |
CA2649290C (en) * | 2006-04-13 | 2017-04-04 | Immunovative Therapies, Ltd. | Allogeneic cell therapy for treatment of opportunistic infection |
US20080112963A1 (en) * | 2006-11-13 | 2008-05-15 | Immunovative Therapies, Ltd. | Ablative immunotherapy |
KR102121492B1 (ko) | 2011-05-03 | 2020-06-11 | 이뮤노베이티브 테라피스, 엘티디. | 면역치료를 사용하는 il-12의 유도 |
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007500217A (ja) * | 2003-05-13 | 2007-01-11 | マイケル ハル−ノイ, | 同種異系細胞治療:ミラー効果 |
JP2007526314A (ja) * | 2004-03-01 | 2007-09-13 | イミュノバティブ セラピーズ, リミテッド | 細胞治療処方方法および組成物 |
JP2010509337A (ja) * | 2006-11-13 | 2010-03-25 | イミュノバティブ セラピーズ, リミテッド | 切除的免疫療法 |
JP2010536330A (ja) * | 2007-08-16 | 2010-12-02 | セル メト リサーチ ゲゼルシャフト ミット ベシュレンクテル ハフツング | 樹状細胞 |
WO2009135199A2 (en) * | 2008-05-02 | 2009-11-05 | Immunovative Therapies, Ltd. | Vaccine compositions and methods |
Non-Patent Citations (2)
Title |
---|
LEUKEMIA RESEARCH, vol. 32, no. 12, JPN6014050673, 2008, pages 1903 - 1913, ISSN: 0003277644 * |
埼玉医科大学雑誌, vol. 33(3,4), JPN6017024185, 2006, pages 67 - 72, ISSN: 0003588955 * |
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JP6393186B2 (ja) | 2018-09-19 |
EP2704732A2 (en) | 2014-03-12 |
CN109876138A (zh) | 2019-06-14 |
EP2704732B1 (en) | 2020-03-04 |
US20160089433A1 (en) | 2016-03-31 |
JP6615148B2 (ja) | 2019-12-04 |
EP2704732A4 (en) | 2015-02-25 |
JP2017141287A (ja) | 2017-08-17 |
BR112013028285A2 (pt) | 2017-01-10 |
AU2019204699A1 (en) | 2019-07-18 |
KR102121492B1 (ko) | 2020-06-11 |
AU2017204058A1 (en) | 2017-07-13 |
US11045541B2 (en) | 2021-06-29 |
WO2012151279A2 (en) | 2012-11-08 |
US20210268106A1 (en) | 2021-09-02 |
US20240148865A1 (en) | 2024-05-09 |
CN103687602A (zh) | 2014-03-26 |
AU2012250807A1 (en) | 2013-12-12 |
CA2838046A1 (en) | 2012-11-08 |
CA2838046C (en) | 2023-03-07 |
US20130101551A1 (en) | 2013-04-25 |
IL229177B (en) | 2020-07-30 |
US9233156B2 (en) | 2016-01-12 |
KR20140041517A (ko) | 2014-04-04 |
SG194753A1 (en) | 2013-12-30 |
IL229177A0 (en) | 2013-12-31 |
WO2012151279A3 (en) | 2012-12-20 |
US11883490B2 (en) | 2024-01-30 |
SG10201901391RA (en) | 2019-03-28 |
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