JP4184808B2 - 遺伝子改変されたyt細胞系及びその使用 - Google Patents
遺伝子改変されたyt細胞系及びその使用 Download PDFInfo
- Publication number
- JP4184808B2 JP4184808B2 JP2002585617A JP2002585617A JP4184808B2 JP 4184808 B2 JP4184808 B2 JP 4184808B2 JP 2002585617 A JP2002585617 A JP 2002585617A JP 2002585617 A JP2002585617 A JP 2002585617A JP 4184808 B2 JP4184808 B2 JP 4184808B2
- Authority
- JP
- Japan
- Prior art keywords
- cell line
- cell
- receptor
- line according
- cells
- 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.)
- Expired - Fee Related
Links
- 210000004027 cell Anatomy 0.000 claims abstract description 86
- 108020003175 receptors Proteins 0.000 claims abstract description 38
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 18
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 15
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 13
- 239000012634 fragment Substances 0.000 claims abstract description 7
- 108091008874 T cell receptors Proteins 0.000 claims abstract description 5
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims abstract description 5
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 claims description 15
- 230000012010 growth Effects 0.000 claims description 4
- 238000003745 diagnosis Methods 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- 238000004520 electroporation Methods 0.000 claims description 2
- 239000000941 radioactive substance Substances 0.000 claims description 2
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 claims 2
- 208000031295 Animal disease Diseases 0.000 claims 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims 1
- 230000002494 anti-cea effect Effects 0.000 claims 1
- 239000000427 antigen Substances 0.000 claims 1
- 108091007433 antigens Proteins 0.000 claims 1
- 102000036639 antigens Human genes 0.000 claims 1
- 230000001363 autoimmune Effects 0.000 claims 1
- 238000002512 chemotherapy Methods 0.000 claims 1
- 108700010039 chimeric receptor Proteins 0.000 claims 1
- 230000001472 cytotoxic effect Effects 0.000 claims 1
- 210000002865 immune cell Anatomy 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 abstract description 4
- 230000009089 cytolysis Effects 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 4
- 210000004369 blood Anatomy 0.000 abstract description 3
- 239000008280 blood Substances 0.000 abstract description 3
- 210000000130 stem cell Anatomy 0.000 abstract description 3
- 238000010353 genetic engineering Methods 0.000 abstract description 2
- 230000009385 viral infection Effects 0.000 abstract description 2
- 238000004140 cleaning Methods 0.000 abstract 1
- 238000010926 purge Methods 0.000 abstract 1
- 102000005962 receptors Human genes 0.000 description 20
- 102000012406 Carcinoembryonic Antigen Human genes 0.000 description 13
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 230000002101 lytic effect Effects 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 238000011579 SCID mouse model Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- SJHPCNCNNSSLPL-CSKARUKUSA-N (4e)-4-(ethoxymethylidene)-2-phenyl-1,3-oxazol-5-one Chemical compound O1C(=O)C(=C/OCC)\N=C1C1=CC=CC=C1 SJHPCNCNNSSLPL-CSKARUKUSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 101000839073 Homo sapiens Heterogeneous nuclear ribonucleoprotein M Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 206010042135 Stomatitis necrotising Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 201000008585 noma Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Images
Classifications
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0646—Natural killers cells [NK], NKT cells
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4613—Natural-killer cells [NK or NK-T]
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/46448—Cancer antigens from embryonic or fetal origin
- A61K39/464482—Carcinoembryonic antigen [CEA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5156—Animal cells expressing foreign proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterized by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
- A61K2239/50—Colon
-
- 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
- C12N2510/00—Genetically modified cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Reproductive Health (AREA)
- Virology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Communicable Diseases (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
本発明は、受容体遺伝子が組み込まれ、そして、例えば、腫瘍、腫瘍転移、自己免疫疾患、ウイルス感染の治療及び診断において、及び血液幹細胞の調製の浄化(一掃)のために使用されうる、遺伝子改変されたYT細胞系に関する。出願の分野は医薬及び製薬産業内である。
−YT細胞系は受容体の遺伝子移入に適合しており、そして受容体遺伝子のトランスファーのために、例えば、腫瘍細胞及び他の標的細胞の認識及び溶解からなる新たな特性を得る。
−上記細胞系はしたがってそれぞれの受容体を選択する方法によりさまざまな腫瘍細胞及び他の標的細胞型に適合されうる。
結腸癌細胞に局在する癌胎児抗原Carcinoembyonic Antigen(CEA)の構造を特異的に認識する受容体が構築された。この受容体の遺伝子は遺伝子トランスファー法としてのエレクトロポーレーションでYT細胞系に統合された。
上記受容体のN’末端にYT細胞の表面上の受容体発現に必要とされるシグナルペプチドがある。上記受容体は柔軟なペプチドリンカーにより結合される抗体(示された実施例中のヒト化CEA特異的抗体BW431)の変動する領域、上記scFv断片及び細胞膜(示される実施例中のヒト抗体(IgG−Fc)のFc部分)の間のスペーサー、及びヒトT細胞受容体のζ−鎖のシグナル誘導部分からなる特異的単鎖Fv−(scFv−)断片からなる。
上記YT細胞系はヒトCEAに特異的である受容体scBW431−hFcζの遺伝子移入により改変された。上記YT細胞の細胞毒性はそれらの表面上にヒトCEAを提示する、細胞系a)MC32Aに対して、及び結腸癌細胞系b)LS174T及びc)SW1222に対して試験された。ブランクベクター(mock)又は腫瘍細胞構造を認識することができない融合受容体scPhOx−hFcζでトランスフェクトされたYT細胞はコントロールとして役割を果たした。
0日目、MC32A腫瘍細胞はCEA特異的YT細胞(YT−scBW431−hFcζ)又はphOx−特異的YT細胞(YT−scPhOx−hFcζ)と共に又はYT細胞なしにNod/SCIDマウスの皮膚下に注入された。使用されたYT細胞はさらなる成長を妨げるために以前に放射に暴露された。図はa)腫瘍成長、及びb)上記細胞の注入後の生存率を示す。1cm3より大きい腫瘍を有する動物は動物保護規則を遵守して殺し、そして死亡したものとして分類した。
Claims (15)
- 遺伝子移入により改変され、かつ、ヒト及び動物の疾患の治療及び診断において使用されるYT細胞系であって、ここで、標的細胞を特異的に認識する抗CEA単鎖可変断片とCD3ζのキメラ受容体をコードする外来遺伝子が組み込まれ、かつ、当該標的細胞は当該YT細胞系により攻撃されることができる細胞である。ことを特徴とする前記YT細胞系。
- 前記受容体が、前記標的細胞上の構造を特異的に認識する認識ドメインを含むことを特徴とする、請求項1に記載のYT細胞系。
- 前記受容体が、腫瘍細胞上の構造を特異的に認識する認識ドメインを含むことを特徴とする、請求項1に記載のYT細胞系。
- 前記受容体が、ウイルス感染細胞上の構造を特異的に認識する認識ドメインを含むことを特徴とする、請求項1に記載のYT細胞系。
- 前記受容体が、自己免疫反応性免疫細胞上の構造を特異的に認識する認識ドメインを含むことを特徴とする、請求項1に記載のYT細胞系。
- 前記受容体ドメインが、腫瘍又は標的細胞に特異的な抗体の可変領域であって単鎖Fv断片を含むものから成ることを特徴とする、請求項1に記載のYT細胞系。
- 前記導入された受容体が、前記YT細胞系の細胞毒性活性を誘導するシグナルを仲介することができるシグナル鎖をさらに含むことを特徴とする、請求項1に記載のYT細胞系。
- 前記導入された受容体のシグナル鎖が、ヒトT細胞受容体のゼータ−鎖に由来することを特徴とする、請求項1に記載のYT細胞系。
- 前記導入された受容体のシグナル鎖が、リンカー・ドメインより前記認識ドメインに結合されることを特徴とする、請求項1に記載のYT細胞系。
- 前記リンカー・ドメインが、ヒトIgG−Fc部に由来することを特徴とする、請求項1に記載のYT細胞系。
- 前記受容体ドメインが、ヒト腫瘍抗原Carcinoembryonic Antigen癌胎児抗原(CEA)、 mucin又はCD33に特異的に結合することを特徴とする、請求項1に記載のYT細胞系。
- 前記YT細胞系、さらなる増殖を妨ぐためにガンマ照射に晒されることを特徴とする、請求項1に記載のYT細胞系。
- 1又は数個の自殺遺伝子が前記YT細胞系に追加的に導入され、そして当該自殺遺伝子の前記細胞系内への導入が、当該細胞系を特定の医薬/化学療法/物質の作用に対して感受性にさせることを特徴とする、請求項1に記載のYT細胞系。
- 受容体構築物又は複数の受容体構築物をコードする遺伝子がエレクトロポーレーションにより前記細胞内に導入されることを特徴とする、請求項1に記載のYT細胞系。
- 前記YT細胞系が、染料又は放射活性物質で標識されることを特徴とする、請求項1に記載のYT細胞系。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10121113A DE10121113A1 (de) | 2001-04-28 | 2001-04-28 | Genmodifizierte YT Zelllinie und ihre Verwendung |
PCT/DE2002/001437 WO2002088336A2 (de) | 2001-04-28 | 2002-04-18 | Genmodifizierte yt zelllinie und ihre verwendung |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2004528036A JP2004528036A (ja) | 2004-09-16 |
JP4184808B2 true JP4184808B2 (ja) | 2008-11-19 |
Family
ID=7683238
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2002585617A Expired - Fee Related JP4184808B2 (ja) | 2001-04-28 | 2002-04-18 | 遺伝子改変されたyt細胞系及びその使用 |
Country Status (7)
Country | Link |
---|---|
US (1) | US20040120935A1 (ja) |
EP (1) | EP1383872B1 (ja) |
JP (1) | JP4184808B2 (ja) |
AT (1) | ATE310805T1 (ja) |
CA (1) | CA2445593C (ja) |
DE (2) | DE10121113A1 (ja) |
WO (1) | WO2002088336A2 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BRPI0313739B8 (pt) | 2002-08-13 | 2021-07-27 | N Dia Inc | método para detectar infiltração de líquido amniótico em secreções vaginais e dispositivo para realizar um método de detecção |
DE102010044321A1 (de) * | 2010-09-03 | 2012-03-08 | Gabriele Pecher | Neue Verwendung einer YT-Zelllinie zur Therapie von malignen Erkrankungen und Virusinfektionen sowie zur Produktion von Interferon gamma |
JP6465812B2 (ja) | 2013-01-02 | 2019-02-06 | キアゲン・サイエンシズ・エル・エル・シー | 妊婦において分娩までの時間を予測するための方法 |
DE102015005097A1 (de) * | 2015-04-22 | 2016-10-27 | Gabriele Pecher | Chimärer Antigenrezeptor (CAR) zur Krebsimmuntherapie |
US10935555B2 (en) | 2016-12-22 | 2021-03-02 | Qiagen Sciences, Llc | Determining candidate for induction of labor |
US10656164B2 (en) | 2016-12-22 | 2020-05-19 | Qiagen Sciences, Llc | Screening asymptomatic pregnant woman for preterm birth |
WO2018129199A1 (en) | 2017-01-04 | 2018-07-12 | Nova Southeastern University | Natural killer (nk) cells expressing an antigen-specific functional t cell receptor (tcr) complex, methods for production thereof, and methods for therapeutic use thereof |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8211422B2 (en) * | 1992-03-18 | 2012-07-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric receptor genes and cells transformed therewith |
PT758394E (pt) * | 1994-05-02 | 2003-04-30 | Bernd Groner | Proteina bifuncional sua preparacao e utilizacao |
ES2263205T3 (es) * | 1997-04-30 | 2006-12-01 | Hans Klingemann | Estirpes celulares citoliticas naturales y metodos de uso. |
US6410319B1 (en) * | 1998-10-20 | 2002-06-25 | City Of Hope | CD20-specific redirected T cells and their use in cellular immunotherapy of CD20+ malignancies |
-
2001
- 2001-04-28 DE DE10121113A patent/DE10121113A1/de not_active Withdrawn
-
2002
- 2002-04-18 CA CA2445593A patent/CA2445593C/en not_active Expired - Fee Related
- 2002-04-18 AT AT02742682T patent/ATE310805T1/de active
- 2002-04-18 JP JP2002585617A patent/JP4184808B2/ja not_active Expired - Fee Related
- 2002-04-18 EP EP02742682A patent/EP1383872B1/de not_active Expired - Lifetime
- 2002-04-18 US US10/476,007 patent/US20040120935A1/en not_active Abandoned
- 2002-04-18 DE DE50205030T patent/DE50205030D1/de not_active Expired - Lifetime
- 2002-04-18 WO PCT/DE2002/001437 patent/WO2002088336A2/de active IP Right Grant
Also Published As
Publication number | Publication date |
---|---|
EP1383872B1 (de) | 2005-11-23 |
DE50205030D1 (de) | 2005-12-29 |
DE10121113A1 (de) | 2002-10-31 |
CA2445593C (en) | 2013-07-09 |
WO2002088336A2 (de) | 2002-11-07 |
ATE310805T1 (de) | 2005-12-15 |
JP2004528036A (ja) | 2004-09-16 |
US20040120935A1 (en) | 2004-06-24 |
CA2445593A1 (en) | 2002-11-07 |
EP1383872A2 (de) | 2004-01-28 |
WO2002088336A3 (de) | 2003-04-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6997267B2 (ja) | 抗ヒトパピローマウイルス16 e7 t細胞受容体 | |
EP0679093B1 (en) | Methods of delivering agents to target cells | |
Dasgupta et al. | Inhibition of NK cell activity through TGF-β1 by down-regulation of NKG2D in a murine model of head and neck cancer | |
AU2014225788B2 (en) | Engager cells for immunotherapy | |
JP3786695B2 (ja) | 修飾した抗原性免疾グロブリンによるt細胞の活性化 | |
Zhao et al. | Oncolytic adenovirus: prospects for cancer immunotherapy | |
CN105407902A (zh) | 溶瘤病毒 | |
Nosaki et al. | A novel, polymer-coated oncolytic measles virus overcomes immune suppression and induces robust antitumor activity | |
JP2021521818A (ja) | 有効な免疫療法のための抗原−サイトカイン複合体に用いた免疫エフェクター細胞及び分子アダプター | |
JPH07502026A (ja) | ウイルス抗体複合体 | |
CN110730908A (zh) | 表达前列腺特异性膜抗原(psma)或其修饰形式的工程化细胞及相关方法 | |
CN110684117B (zh) | 一种car嵌合抗原受体序列及应用其的car-nk细胞 | |
JP4184808B2 (ja) | 遺伝子改変されたyt細胞系及びその使用 | |
CN109415706A (zh) | 假型化的溶瘤弹状病毒及其在组合治疗中的应用 | |
CN107488636A (zh) | 一种携带分子开关的抗her2嵌合抗原受体修饰的免疫细胞及其应用 | |
CN109762068A (zh) | 一种可靶向ctla4和pd-1的单基因双特异性抗体及其应用 | |
CN110981960B (zh) | 一种嵌合抗原受体(car)及其应用 | |
CN107164412A (zh) | 一种安全型抗cea嵌合抗原受体修饰t细胞的制备方法及其应用 | |
Hutzen et al. | Advances in the design and development of oncolytic measles viruses | |
CN114026118A (zh) | 通过铰链结构域增强多肽和嵌合抗原受体 | |
Kvorjak et al. | Conditional control of universal CAR T cells by cleavable OFF-switch adaptors | |
Paul et al. | Tumor gene therapy by MVA-mediated expression of T-cell–stimulating antibodies | |
JP2004507205A (ja) | Ca19−9抗原陽性細胞の検出および除去のためのポリペプチド | |
CN112048021A (zh) | 一种靶向ror2的嵌合抗原受体、表达基因、表达载体、t细胞及其应用 | |
US20210309750A1 (en) | Enhanced Delivery of Drugs and Other Compounds to the Brain and Other Tissues |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050325 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20071211 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080310 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080317 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080611 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20080805 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20080904 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110912 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120912 Year of fee payment: 4 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120912 Year of fee payment: 4 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130912 Year of fee payment: 5 |
|
LAPS | Cancellation because of no payment of annual fees |