JP2018506995A5 - - Google Patents
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- JP2018506995A5 JP2018506995A5 JP2017562971A JP2017562971A JP2018506995A5 JP 2018506995 A5 JP2018506995 A5 JP 2018506995A5 JP 2017562971 A JP2017562971 A JP 2017562971A JP 2017562971 A JP2017562971 A JP 2017562971A JP 2018506995 A5 JP2018506995 A5 JP 2018506995A5
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- JP
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- Prior art keywords
- cells
- transgene
- cell
- sequence encoding
- dhfr
- 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.)
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- 210000001744 T-lymphocyte Anatomy 0.000 claims description 130
- 238000000034 method Methods 0.000 claims description 102
- 108700019146 Transgenes Proteins 0.000 claims description 78
- 210000004027 cell Anatomy 0.000 claims description 66
- 230000009261 transgenic effect Effects 0.000 claims description 65
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims description 48
- 102100024746 Dihydrofolate reductase Human genes 0.000 claims description 46
- 108020001096 dihydrofolate reductase Proteins 0.000 claims description 46
- 101000809797 Homo sapiens Thymidylate synthase Proteins 0.000 claims description 42
- 102100038618 Thymidylate synthase Human genes 0.000 claims description 42
- 239000002773 nucleotide Substances 0.000 claims description 40
- 125000003729 nucleotide group Chemical group 0.000 claims description 40
- 210000003289 regulatory T cell Anatomy 0.000 claims description 40
- 230000015572 biosynthetic process Effects 0.000 claims description 28
- 238000003786 synthesis reaction Methods 0.000 claims description 28
- 239000003112 inhibitor Substances 0.000 claims description 26
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims description 24
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims description 24
- 229940104230 thymidine Drugs 0.000 claims description 24
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 22
- 229960000485 methotrexate Drugs 0.000 claims description 22
- 210000000581 natural killer T-cell Anatomy 0.000 claims description 20
- 108090000623 proteins and genes Proteins 0.000 claims description 20
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 claims description 16
- 108090000695 Cytokines Proteins 0.000 claims description 14
- 102000004127 Cytokines Human genes 0.000 claims description 14
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 14
- 229960002949 fluorouracil Drugs 0.000 claims description 14
- 150000007523 nucleic acids Chemical group 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 12
- 210000003162 effector t lymphocyte Anatomy 0.000 claims description 12
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims description 12
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 10
- IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 claims description 10
- 210000002203 alpha-beta t lymphocyte Anatomy 0.000 claims description 10
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims description 10
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 claims description 10
- 210000002443 helper t lymphocyte Anatomy 0.000 claims description 10
- 210000003071 memory t lymphocyte Anatomy 0.000 claims description 10
- 210000004877 mucosa Anatomy 0.000 claims description 10
- 108020004707 nucleic acids Proteins 0.000 claims description 10
- 102000039446 nucleic acids Human genes 0.000 claims description 10
- 229960005079 pemetrexed Drugs 0.000 claims description 10
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 claims description 10
- 229960004432 raltitrexed Drugs 0.000 claims description 10
- 108020004999 messenger RNA Proteins 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 108091033319 polynucleotide Proteins 0.000 claims description 8
- 102000040430 polynucleotide Human genes 0.000 claims description 8
- 239000002157 polynucleotide Substances 0.000 claims description 8
- 230000001629 suppression Effects 0.000 claims description 8
- 102000015731 Peptide Hormones Human genes 0.000 claims description 6
- 108010038988 Peptide Hormones Proteins 0.000 claims description 6
- 108091008874 T cell receptors Proteins 0.000 claims description 6
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 6
- 229940014144 folate Drugs 0.000 claims description 6
- 235000019152 folic acid Nutrition 0.000 claims description 6
- 239000011724 folic acid Substances 0.000 claims description 6
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 6
- 239000000813 peptide hormone Substances 0.000 claims description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 4
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 claims description 4
- 102000019034 Chemokines Human genes 0.000 claims description 4
- 108010012236 Chemokines Proteins 0.000 claims description 4
- 108091026890 Coding region Proteins 0.000 claims description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 4
- 239000011324 bead Substances 0.000 claims description 4
- 230000000779 depleting effect Effects 0.000 claims description 4
- 235000008191 folinic acid Nutrition 0.000 claims description 4
- 239000011672 folinic acid Substances 0.000 claims description 4
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 4
- 238000002955 isolation Methods 0.000 claims description 4
- 229960001691 leucovorin Drugs 0.000 claims description 4
- 210000004962 mammalian cell Anatomy 0.000 claims description 4
- 102000004039 Caspase-9 Human genes 0.000 claims description 2
- 108090000566 Caspase-9 Proteins 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 108091023040 Transcription factor Proteins 0.000 claims description 2
- 102000040945 Transcription factor Human genes 0.000 claims description 2
- 229940126575 aminoglycoside Drugs 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims description 2
- 239000003102 growth factor Substances 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 230000002062 proliferating effect Effects 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 238000010187 selection method Methods 0.000 claims description 2
- 230000001988 toxicity Effects 0.000 claims description 2
- 231100000419 toxicity Toxicity 0.000 claims description 2
- 230000006870 function Effects 0.000 claims 1
- 108700026220 vif Genes Proteins 0.000 claims 1
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562120329P | 2015-02-24 | 2015-02-24 | |
| US62/120,329 | 2015-02-24 | ||
| US201562120790P | 2015-02-25 | 2015-02-25 | |
| US62/120,790 | 2015-02-25 | ||
| US201562175794P | 2015-06-15 | 2015-06-15 | |
| US62/175,794 | 2015-06-15 | ||
| PCT/US2016/019288 WO2016138091A2 (en) | 2015-02-24 | 2016-02-24 | Selection methods for genetically-modified t cells |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018506995A JP2018506995A (ja) | 2018-03-15 |
| JP2018506995A5 true JP2018506995A5 (enExample) | 2019-03-14 |
| JP6947647B2 JP6947647B2 (ja) | 2021-10-13 |
Family
ID=56464271
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017562971A Active JP6947647B2 (ja) | 2015-02-24 | 2016-02-24 | 遺伝子改変ｔ細胞の選択方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US10808230B2 (enExample) |
| EP (2) | EP3261656B1 (enExample) |
| JP (1) | JP6947647B2 (enExample) |
| KR (1) | KR20170117095A (enExample) |
| CN (1) | CN107667169B (enExample) |
| AU (2) | AU2016222850B2 (enExample) |
| CA (1) | CA2976126A1 (enExample) |
| WO (1) | WO2016138091A2 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105408473B9 (zh) | 2013-05-14 | 2021-09-17 | 得克萨斯州大学系统董事会 | 工程化嵌合抗原受体(car)t细胞的人应用 |
| WO2015123642A1 (en) | 2014-02-14 | 2015-08-20 | Board Of Regents, The University Of Texas System | Chimeric antigen receptors and methods of making |
| CA2964783C (en) | 2014-11-05 | 2024-01-23 | Board Of Regents, The University Of Texas System | Chimeric antigen receptors (car) to selectively target protein complexes |
| WO2016145146A1 (en) | 2015-03-11 | 2016-09-15 | Board Of Regents, The University Of Texas System | Transposase polypeptides and uses thereof |
| US10633445B2 (en) | 2015-09-15 | 2020-04-28 | Board Of Regents The University Of Texas System | T-cell receptor (TCR)-binding antibodies and uses thereof |
| US11059879B2 (en) | 2015-10-27 | 2021-07-13 | Board Of Regents, The University Of Texas System | Chimeric antigen receptor molecules and uses thereof |
| US11629340B2 (en) | 2017-03-03 | 2023-04-18 | Obsidian Therapeutics, Inc. | DHFR tunable protein regulation |
| US10780119B2 (en) | 2017-05-24 | 2020-09-22 | Effector Therapeutics Inc. | Methods and compositions for cellular immunotherapy |
| CN109136282A (zh) * | 2018-09-30 | 2019-01-04 | 北京鼎成肽源生物技术有限公司 | 一种hafft1细胞的构建方法 |
| CN120555349A (zh) | 2018-11-16 | 2025-08-29 | 拉帕治疗有限公司 | 使用诱导性调节性T（iTREG）细胞进行的ALS治疗 |
| WO2020102726A1 (en) * | 2018-11-16 | 2020-05-22 | Rapa Therapeutics, Llc | Method for manufacturing of human hybrid regulatory t/th2 cells (hybrid treg/th2 cells) from de-differentiated t cells |
| KR102594009B1 (ko) | 2021-02-01 | 2023-10-24 | 서울대학교산학협력단 | 형질전환 생식세포의 제조 방법 및 이를 이용한 형질전환 동물의 제조 방법 |
| WO2023056408A1 (en) * | 2021-09-30 | 2023-04-06 | University Of Southern California | Human hepatocyte culture medium and conditioned medium of in vitro cultured human hepatocytes and uses thereof |
| CN114740196B (zh) * | 2022-04-08 | 2023-04-18 | 中南大学湘雅二医院 | 标志物及其在制备评价机体免疫功能的产品中的应用 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102575227A (zh) * | 2008-10-08 | 2012-07-11 | 英特瑞克斯顿股份有限公司 | 表达多种免疫调节剂的工程改造细胞及其应用 |
| WO2011053750A2 (en) * | 2009-11-02 | 2011-05-05 | Emory University | Drug resistant immunotherapy for treatment of a cancer |
| PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| US8809017B2 (en) * | 2011-05-24 | 2014-08-19 | Agency For Science, Technology And Research | IRES mediated multicistronic vectors |
| WO2013074916A1 (en) | 2011-11-18 | 2013-05-23 | Board Of Regents, The University Of Texas System | Car+ t cells genetically modified to eliminate expression of t- cell receptor and/or hla |
| US9447194B2 (en) * | 2012-02-13 | 2016-09-20 | Seattle Children's Hospital | Bispecific chimeric antigen receptors and encoding polynucleotides thereof |
| CN105408473B9 (zh) | 2013-05-14 | 2021-09-17 | 得克萨斯州大学系统董事会 | 工程化嵌合抗原受体(car)t细胞的人应用 |
| HK1223943A1 (zh) | 2013-05-24 | 2017-08-11 | Board Of Regents, The University Of Texas System | 嵌合的靶向抗原受体的单克隆抗体 |
| WO2015061694A2 (en) | 2013-10-25 | 2015-04-30 | Board Of Regents, The University Of Texas System | Polyclonal gamma delta t cells for immunotherapy |
| JP6976058B2 (ja) * | 2013-11-22 | 2021-12-01 | セレクティスCellectis | 免疫療法のための化学療法薬耐性ｔ細胞を工学的に作製する方法 |
| WO2015123642A1 (en) | 2014-02-14 | 2015-08-20 | Board Of Regents, The University Of Texas System | Chimeric antigen receptors and methods of making |
| RU2016143389A (ru) * | 2014-04-10 | 2018-05-15 | Сиэтл Чилдрен'С Хоспитал (Дба Сиэтл Чилдрен'С Ресёрч Инститьют) | Получение генно-инженерных т-клеток посредством транспозона "спящая красавица" в сочетании с отбором метотрексатом |
| CN106459924A (zh) | 2014-04-23 | 2017-02-22 | 得克萨斯州大学系统董事会 | 用于疗法中的嵌合抗原受体(car)及其制备方法 |
| AU2015249371B2 (en) | 2014-04-24 | 2020-04-30 | Board Of Regents, The University Of Texas System | Application of induced pluripotent stem cells to generate adoptive cell therapy products |
| CA2964783C (en) | 2014-11-05 | 2024-01-23 | Board Of Regents, The University Of Texas System | Chimeric antigen receptors (car) to selectively target protein complexes |
| CA2964785A1 (en) | 2014-11-05 | 2016-05-12 | Board Of Regents, The University Of Texas System | Gene modified immune effector cells and engineered cells for expansion of immune effector cells |
| WO2016145146A1 (en) | 2015-03-11 | 2016-09-15 | Board Of Regents, The University Of Texas System | Transposase polypeptides and uses thereof |
| US10633445B2 (en) | 2015-09-15 | 2020-04-28 | Board Of Regents The University Of Texas System | T-cell receptor (TCR)-binding antibodies and uses thereof |
| US11059879B2 (en) | 2015-10-27 | 2021-07-13 | Board Of Regents, The University Of Texas System | Chimeric antigen receptor molecules and uses thereof |
-
2016
- 2016-02-24 CN CN201680011714.XA patent/CN107667169B/zh active Active
- 2016-02-24 JP JP2017562971A patent/JP6947647B2/ja active Active
- 2016-02-24 EP EP16741163.6A patent/EP3261656B1/en active Active
- 2016-02-24 KR KR1020177024195A patent/KR20170117095A/ko not_active Withdrawn
- 2016-02-24 WO PCT/US2016/019288 patent/WO2016138091A2/en not_active Ceased
- 2016-02-24 CA CA2976126A patent/CA2976126A1/en active Pending
- 2016-02-24 AU AU2016222850A patent/AU2016222850B2/en not_active Ceased
- 2016-02-24 EP EP20191615.2A patent/EP3804741A3/en not_active Withdrawn
- 2016-02-24 US US15/552,821 patent/US10808230B2/en active Active
-
2020
- 2020-09-04 US US17/013,195 patent/US20210054346A1/en not_active Abandoned
-
2021
- 2021-06-02 AU AU2021203606A patent/AU2021203606A1/en not_active Abandoned
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