JP6257655B2 - 末梢血から腫瘍反応性t細胞の濃縮された集団を作製する方法 - Google Patents
末梢血から腫瘍反応性t細胞の濃縮された集団を作製する方法 Download PDFInfo
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Description
本特許出願は、2013年3月1日に出願された米国仮特許出願第61/771,251号の利益を主張し、それは、参照によりその全体が本明細書に組み込まれる。
腫瘍反応性T細胞を用いる養子細胞療法(ACT)は、ある種の癌患者において明確な臨床反応を引き起こし得る。それにもかかわらず、癌及び他の疾病の治療のためにACTを有効に活用するためには、いくつかの障壁が残っている。例えば、末梢血から単離されたT細胞は、十分な腫瘍特異的反応性を示さないことがある。従って、末梢血から腫瘍反応性T細胞の集団を得る方法を改善する必要がある。
本発明の実施の態様は、腫瘍反応性T細胞について濃縮された細胞集団を得る方法を提供し、該方法は:(a)末梢血のサンプルから末梢血単核細胞(PBMCs)の混合集団(bulk population)を得ること;(b)混合集団からPD‐1及び/またはTIM‐3も発現するCD8+T細胞を特異的に選択すること;及び(c)(b)において選択された細胞を、選択されていない細胞から分離して、腫瘍反応性T細胞について濃縮された細胞集団を得ること、を含む。
プログラム細胞死タンパク質1(programmed cell death protein 1,PD‐1;CD279)及び/またはT-細胞イムノグロブリン及びムチンドメイン3(T-cell immunoglobulin and mucin domain 3,TIM‐3)バイオマーカも発現するCD8+細胞を選択することにより、末梢血にある腫瘍反応性T細胞が濃縮されることが分かった。PD‐1及び/またはTIM‐3も発現するCD8+細胞を選択することにより、これらのマーカを発現しないCD8+細胞に比べて、より多数の腫瘍反応性T細胞が有利に濃縮される。
本実施例は、PD‐1、TIM‐3、またはLAG‐3発現に従う、メラノーマ患者の末梢血から単離したT細胞の細胞数をインビトロで増加させた後のインビトロでの自己腫瘍認識を示す。
本実施例は、メラノーマ患者の末梢血から単離し、PD‐1またはTIM‐3発現に従ってソートしたT細胞のインビトロで細胞数を増加させた後のインビトロでの自己腫瘍認識を示す。
Claims (22)
- 腫瘍反応性T細胞について濃縮された細胞集団を得る方法であって、該方法が、
(a)末梢血サンプルから末梢血単核細胞(PBMCs)の混合集団を得ること;
(b)前記混合集団からPD‐1及び/またはTIM‐3も発現するCD8+T細胞を特異的に選択すること;及び
(c)(b)において選択された前記細胞を、選択されていない細胞から分離して、腫瘍反応性T細胞について濃縮された細胞集団を得ること、
を含む、方法。 - 腫瘍反応性T細胞について濃縮された細胞集団を含む医薬組成物を得る方法であって、該方法が、
(a)末梢血サンプルから末梢血単核細胞(PBMCs)の混合集団を得ること;
(b)前記混合集団からPD‐1及び/またはTIM‐3も発現するCD8+T細胞を特異的に選択すること;
(c)(b)において選択された前記細胞を、選択されていない細胞から分離して、腫瘍反応性T細胞について濃縮された細胞集団を得ること;及び
(d)腫瘍反応性T細胞について濃縮された前記細胞集団を医薬上許容される担体と組み合わせて、腫瘍反応性T細胞について濃縮された細胞集団を含む医薬組成物を得ること、
を含む、方法。 - (b)が、前記混合集団からTIM‐3を発現するCD8+T細胞を特異的に選択することを含む、請求項1または2に記載の方法。
- (b)が、前記混合集団からPD‐1を発現するCD8+T細胞を特異的に選択することを含む、請求項1〜3のいずれか1項に記載の方法。
- (b)が、前記混合集団から(i)TIM‐3+/PD‐1+、(ii)TIM‐3-/PD‐1+、または(iii)TIM‐3+/PD‐1-であるCD8+T細胞を特異的に選択することを含む、請求項1または2に記載の方法。
- 腫瘍反応性T細胞について濃縮された前記細胞集団が、自己腫瘍認識についてスクリーニングをすることなく得られる、請求項1〜5のいずれか1項に記載の方法。
- T細胞の混合集団が、(b)より前に非特異的に刺激されない、請求項1〜6のいずれか1項に記載の方法。
- (c)において得られた前記濃縮された細胞集団においてT細胞の数を増加させることを更に含む、請求項1〜7のいずれか1項に記載の方法。
- TWS119、インターロイキン(IL‐21)、IL‐12、IL‐15、IL‐7、形質転換成長因子(TGF)ベータ、及びAKTインヒビター(AKTi)のいずれか1以上の存在下で、(c)において得られた前記濃縮された細胞集団を培養することを更に含む、請求項1〜8のいずれか1項に記載の方法。
- 腫瘍抗原及び/または自己腫瘍T細胞を用いて、(c)において得られた前記濃縮された細胞集団を刺激することを更に含む、請求項1〜9のいずれか1項に記載の方法。
- IL‐12、IL‐7、IL‐15、IL‐2、IL‐21、mir155、及び抗PD‐1 siRNAのいずれか1以上をコードするヌクレオチド配列を、(c)において得られた前記濃縮された集団の細胞に形質導入またはトランスフェクトすることを更に含む、請求項1〜10のいずれか1項に記載の方法。
- 腫瘍反応性T細胞について濃縮された細胞集団を哺乳動物へ投与するための組成物であって、
(a)末梢血のサンプルから末梢血単核細胞(PBMCs)の混合集団を得ること;
(b)前記混合集団からPD‐1及び/またはTIM‐3も発現するCD8+T細胞を特異的に選択すること;及び
(c)(b)において選択された前記細胞を、選択されていない細胞から分離して、腫瘍反応性T細胞について濃縮された細胞集団を得ること、
を含む方法によって腫瘍反応性T細胞について濃縮された細胞集団を含む、組成物。 - (b)が、前記混合集団からTIM‐3を発現するCD8+T細胞を特異的に選択することを含む、請求項12に記載の組成物。
- (b)が、前記混合集団からPD‐1を発現するCD8+T細胞を特異的に選択することを含む、請求項12に記載の組成物。
- (b)が、前記混合集団から(i)TIM‐3+/PD‐1+、(ii)TIM‐3-/PD‐1+、または(iii)TIM‐3+/PD‐1-であるCD8+T細胞を特異的に選択することを含む、請求項12に記載の組成物。
- 腫瘍反応性T細胞について濃縮された前記細胞集団が、自己腫瘍認識についてスクリーニングをすることなく得られる、請求項12〜15のいずれか1項に記載の組成物。
- T細胞の混合集団が、(b)より前に非特異的に刺激されない、請求項12〜16のいずれか1項に記載の組成物。
- (c)において得られた前記濃縮された細胞集団においてT細胞の数を増加させることを更に含む、請求項12〜17のいずれか1項に記載の組成物。
- TWS119、インターロイキン(IL‐21)、IL‐12、IL‐15、IL‐7、形質転換成長因子(TGF)ベータ、及びAKTインヒビター(AKTi)のいずれか1以上の存在下で、(c)において得られた前記濃縮された細胞集団を培養することを更に含む、請求項12〜18のいずれか1項に記載の組成物。
- 腫瘍抗原及び/または自己腫瘍T細胞を用いて、(c)において得られた前記濃縮された細胞集団を刺激することを更に含む、請求項12〜19のいずれか1項に記載の組成物。
- IL‐12、IL‐7、IL‐15、IL‐2、IL‐21、mir155、及び抗PD‐1 siRNAのいずれか1以上をコードするヌクレオチド配列を、(c)において得られた前記濃縮された集団の細胞に形質導入またはトランスフェクトすることを更に含む、請求項12〜20のいずれか1項に記載の組成物。
- 癌の治療または予防のための組成物であって、請求項1及び3〜11のいずれか1項に記載の前記方法によって得られた、腫瘍反応性T細胞について濃縮された細胞集団、請求項2〜11のいずれか1項に記載の方法によって得られた医薬組成物、または請求項12〜21のいずれか1項に記載の組成物を含む、組成物。
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Families Citing this family (77)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101330830B (zh) | 2005-10-18 | 2016-01-20 | 国家犹太健康中心 | 条件无限增殖化长期干细胞和制备和使用所述细胞的方法 |
CA2723114C (en) | 2008-05-16 | 2018-02-27 | Taiga Biotechnologies, Inc. | Antibodies and processes for preparing the same |
ES2681478T3 (es) | 2008-08-28 | 2018-09-13 | Taiga Biotechnologies, Inc. | Moduladores de MYC, métodos de uso de los mismos y métodos para identificar agentes que modulan MYC |
CN114645015A (zh) | 2012-07-20 | 2022-06-21 | 泰加生物工艺学公司 | 造血区室的增强的重建和自动重建 |
EP2961416B1 (en) | 2013-03-01 | 2019-11-13 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Methods of producing enriched populations of tumor reactive t cells from peripheral blood |
US10272115B2 (en) | 2013-03-11 | 2019-04-30 | Taiga Biotechnologies, Inc. | Production and use of red blood cells |
US10801070B2 (en) | 2013-11-25 | 2020-10-13 | The Broad Institute, Inc. | Compositions and methods for diagnosing, evaluating and treating cancer |
WO2015085147A1 (en) | 2013-12-05 | 2015-06-11 | The Broad Institute Inc. | Polymorphic gene typing and somatic change detection using sequencing data |
CA2934073A1 (en) | 2013-12-20 | 2015-06-25 | The Broad Institute, Inc. | Combination therapy with neoantigen vaccine |
EP3154350B1 (en) | 2014-04-10 | 2024-03-27 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy |
JP6599450B2 (ja) | 2014-10-02 | 2019-10-30 | アメリカ合衆国 | がん特異的突然変異に対し抗原特異性を有するt細胞を単離する方法 |
EP3200818B1 (en) * | 2014-10-02 | 2022-06-08 | The United States of America, as represented by the Secretary, Department of Health and Human Services | Methods of isolating t cell receptors having antigenic specificity for a cancer-specific mutation |
US10975442B2 (en) | 2014-12-19 | 2021-04-13 | Massachusetts Institute Of Technology | Molecular biomarkers for cancer immunotherapy |
EP3757211A1 (en) | 2014-12-19 | 2020-12-30 | The Broad Institute, Inc. | Methods for profiling the t-cell-receptor repertoire |
AU2016258845B2 (en) | 2015-05-01 | 2022-03-10 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods of isolating T cells and T cell receptors having antigenic specificity for a cancer-specific mutation from peripheral blood |
IL302102A (en) | 2015-05-20 | 2023-06-01 | Dana Farber Cancer Inst Inc | shared neoantigens |
CN104946589A (zh) * | 2015-07-07 | 2015-09-30 | 英普乐孚生物技术(上海)有限公司 | 一种肿瘤特异性til细胞的分离培养方法 |
US20190255107A1 (en) | 2015-10-09 | 2019-08-22 | The Brigham And Women's Hospital, Inc. | Modulation of novel immune checkpoint targets |
WO2017075451A1 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by detecting and targeting pou2af1 |
WO2017075465A1 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by detecting and targeting gata3 |
WO2017075478A2 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by use of immune cell gene signatures |
AU2016355178B9 (en) | 2015-11-19 | 2019-05-30 | Massachusetts Institute Of Technology | Lymphocyte antigen CD5-like (CD5L)-interleukin 12B (p40) heterodimers in immunity |
GB201522097D0 (en) | 2015-12-15 | 2016-01-27 | Cellular Therapeutics Ltd | Cells |
KR102486307B1 (ko) * | 2016-03-17 | 2023-01-09 | 버클리 라잇츠, 인크. | 미세유체 디바이스에서의 t 림프구들의 선택 및 클로닝 |
SG11201900138TA (en) | 2016-07-07 | 2019-02-27 | Iovance Biotherapeutics Inc | Programmed death 1 ligand 1 (pd-l1) binding proteins and methods of use thereof |
US20190262399A1 (en) | 2016-09-07 | 2019-08-29 | The Broad Institute, Inc. | Compositions and methods for evaluating and modulating immune responses |
WO2018067991A1 (en) | 2016-10-07 | 2018-04-12 | The Brigham And Women's Hospital, Inc. | Modulation of novel immune checkpoint targets |
WO2018081473A1 (en) | 2016-10-26 | 2018-05-03 | Iovance Biotherapeutics, Inc. | Restimulation of cryopreserved tumor infiltrating lymphocytes |
TWI788307B (zh) | 2016-10-31 | 2023-01-01 | 美商艾歐凡斯生物治療公司 | 用於擴增腫瘤浸潤性淋巴細胞之工程化人造抗原呈現細胞 |
KR102618948B1 (ko) | 2016-11-17 | 2023-12-27 | 이오반스 바이오테라퓨틱스, 인크. | 잔유 종양 침윤 림프구 및 그의 제조 및 사용 방법 |
US10583156B2 (en) | 2016-12-02 | 2020-03-10 | Taiga Biotechnologies, Inc. | Nanoparticle formulations |
JP2020503351A (ja) | 2017-01-06 | 2020-01-30 | アイオバンス バイオセラピューティクス,インコーポレイテッド | カリウムチャネルアゴニストによる腫瘍浸潤リンパ球の増殖及びその治療的使用 |
GB201700621D0 (en) | 2017-01-13 | 2017-03-01 | Guest Ryan Dominic | Method,device and kit for the aseptic isolation,enrichment and stabilsation of cells from mammalian solid tissue |
EP3574116A1 (en) | 2017-01-24 | 2019-12-04 | The Broad Institute, Inc. | Compositions and methods for detecting a mutant variant of a polynucleotide |
JOP20190224A1 (ar) | 2017-03-29 | 2019-09-26 | Iovance Biotherapeutics Inc | عمليات من أجل إنتاج الخلايا اللمفاوية المرتشحة للأورام واستخداماتها في العلاج المناعي |
US11254913B1 (en) | 2017-03-29 | 2022-02-22 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy |
WO2018183908A1 (en) | 2017-03-31 | 2018-10-04 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating ovarian tumors |
WO2018183921A1 (en) | 2017-04-01 | 2018-10-04 | The Broad Institute, Inc. | Methods and compositions for detecting and modulating an immunotherapy resistance gene signature in cancer |
EP3610266A4 (en) | 2017-04-12 | 2021-04-21 | Massachusetts Eye and Ear Infirmary | TUMOR SIGNATURE OF METASTASIS, COMPOSITIONS OF SUBSTANCES AND USES THEREOF |
CN110662762A (zh) | 2017-05-24 | 2020-01-07 | 诺华股份有限公司 | 抗体细胞因子移植蛋白和用于治疗癌症的方法 |
US11819517B2 (en) | 2017-06-05 | 2023-11-21 | Iovance Biotherapeutics, Inc. | Methods of using tumor infiltrating lymphocytes in double-refractory melanoma |
EP3638218A4 (en) | 2017-06-14 | 2021-06-09 | The Broad Institute, Inc. | COMPOSITIONS AND METHOD OF TARGETING COMPLEMENTING COMPONENT 3 FOR INHIBITION OF TUMOR GROWTH |
WO2019014581A1 (en) | 2017-07-14 | 2019-01-17 | The Broad Institute, Inc. | METHODS AND COMPOSITIONS FOR MODULATING THE ACTIVITY OF A CYTOTOXIC LYMPHOCYTE |
AU2017425657A1 (en) | 2017-08-03 | 2020-02-13 | Taiga Biotechnologies, Inc. | Methods and compositions for the treatment of melanoma |
US10149898B2 (en) | 2017-08-03 | 2018-12-11 | Taiga Biotechnologies, Inc. | Methods and compositions for the treatment of melanoma |
CN109423478A (zh) * | 2017-08-22 | 2019-03-05 | 郑州大学第附属医院 | 一种记忆性t细胞的制备方法 |
WO2019070755A1 (en) | 2017-10-02 | 2019-04-11 | The Broad Institute, Inc. | METHODS AND COMPOSITIONS FOR DETECTING AND MODULATING A GENETIC SIGNATURE OF IMMUNOTHERAPY RESISTANCE IN CANCER |
WO2019084055A1 (en) | 2017-10-23 | 2019-05-02 | Massachusetts Institute Of Technology | CLASSIFICATION OF GENETIC VARIATION FROM UNICELLULAR TRANSCRIPTOMS |
US12018080B2 (en) | 2017-11-13 | 2024-06-25 | The Broad Institute, Inc. | Methods and compositions for treating cancer by targeting the CLEC2D-KLRB1 pathway |
CN108254557B (zh) * | 2017-12-26 | 2019-05-31 | 首都医科大学附属北京地坛医院 | 用cd8阳性的t细胞上pd-1和tigit确定hbv相关原发性肝癌预后的系统 |
US11994512B2 (en) | 2018-01-04 | 2024-05-28 | Massachusetts Institute Of Technology | Single-cell genomic methods to generate ex vivo cell systems that recapitulate in vivo biology with improved fidelity |
US11713446B2 (en) | 2018-01-08 | 2023-08-01 | Iovance Biotherapeutics, Inc. | Processes for generating TIL products enriched for tumor antigen-specific T-cells |
US11957695B2 (en) | 2018-04-26 | 2024-04-16 | The Broad Institute, Inc. | Methods and compositions targeting glucocorticoid signaling for modulating immune responses |
BR112020021660A2 (pt) | 2018-04-27 | 2021-02-02 | Iovance Biotherapeutics, Inc. | métodos para expandir linfócitos infiltrantes de tumor e para tratar um indivíduo com câncer, população de linfócitos infiltrantes de tumor, e, composição de criopreservação |
US20210371932A1 (en) | 2018-06-01 | 2021-12-02 | Massachusetts Institute Of Technology | Methods and compositions for detecting and modulating microenvironment gene signatures from the csf of metastasis patients |
US12036240B2 (en) | 2018-06-14 | 2024-07-16 | The Broad Institute, Inc. | Compositions and methods targeting complement component 3 for inhibiting tumor growth |
WO2020072700A1 (en) | 2018-10-02 | 2020-04-09 | Dana-Farber Cancer Institute, Inc. | Hla single allele lines |
US20210379057A1 (en) | 2018-10-16 | 2021-12-09 | Massachusetts Institute Of Technology | Nutlin-3a for use in treating a mycobacterium tuberculosis infection |
WO2020131586A2 (en) | 2018-12-17 | 2020-06-25 | The Broad Institute, Inc. | Methods for identifying neoantigens |
US11739156B2 (en) | 2019-01-06 | 2023-08-29 | The Broad Institute, Inc. Massachusetts Institute of Technology | Methods and compositions for overcoming immunosuppression |
US20220154282A1 (en) | 2019-03-12 | 2022-05-19 | The Broad Institute, Inc. | Detection means, compositions and methods for modulating synovial sarcoma cells |
US20220142948A1 (en) | 2019-03-18 | 2022-05-12 | The Broad Institute, Inc. | Compositions and methods for modulating metabolic regulators of t cell pathogenicity |
CN110452870A (zh) * | 2019-05-20 | 2019-11-15 | 河南省肿瘤医院 | 一种肿瘤特异性t细胞的分离培养方法及由其获得的产品 |
US20220235340A1 (en) | 2019-05-20 | 2022-07-28 | The Broad Institute, Inc. | Novel crispr-cas systems and uses thereof |
WO2020243371A1 (en) | 2019-05-28 | 2020-12-03 | Massachusetts Institute Of Technology | Methods and compositions for modulating immune responses |
US20220282333A1 (en) | 2019-08-13 | 2022-09-08 | The General Hospital Corporation | Methods for predicting outcomes of checkpoint inhibition and treatment thereof |
US20220298501A1 (en) | 2019-08-30 | 2022-09-22 | The Broad Institute, Inc. | Crispr-associated mu transposase systems |
US11981922B2 (en) | 2019-10-03 | 2024-05-14 | Dana-Farber Cancer Institute, Inc. | Methods and compositions for the modulation of cell interactions and signaling in the tumor microenvironment |
US11793787B2 (en) | 2019-10-07 | 2023-10-24 | The Broad Institute, Inc. | Methods and compositions for enhancing anti-tumor immunity by targeting steroidogenesis |
KR20220119439A (ko) | 2019-12-20 | 2022-08-29 | 인스틸 바이오 유케이 리미티드 | 종양 침윤 림프구를 분리하기 위한 장치 및 방법 및 그것의 용도 |
JP2020143057A (ja) * | 2020-04-01 | 2020-09-10 | アメリカ合衆国 | がん特異的突然変異に対し抗原特異性を有するt細胞受容体を単離する方法 |
WO2021216920A1 (en) | 2020-04-22 | 2021-10-28 | Iovance Biotherapeutics, Inc. | Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy |
CN111850119B (zh) * | 2020-06-04 | 2022-08-26 | 吴式琇 | 定量检测bst1、stab1和tlr4基因表达水平的方法及应用 |
RU2752973C1 (ru) * | 2020-10-12 | 2021-08-11 | Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт фундаментальной и клинической иммунологии" | Способ определения качественных параметров иммуносупрессивных клеток у онкологических пациентов |
WO2023064928A2 (en) | 2021-10-14 | 2023-04-20 | Arsenal Biosciences, Inc. | Immune cells having co-expressed shrnas and logic gate systems |
WO2023201369A1 (en) | 2022-04-15 | 2023-10-19 | Iovance Biotherapeutics, Inc. | Til expansion processes using specific cytokine combinations and/or akti treatment |
WO2024124044A1 (en) | 2022-12-07 | 2024-06-13 | The Brigham And Women’S Hospital, Inc. | Compositions and methods targeting sat1 for enhancing anti¬ tumor immunity during tumor progression |
Family Cites Families (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5229115A (en) | 1990-07-26 | 1993-07-20 | Immunex Corporation | Adoptive immunotherapy with interleukin-7 |
US5834441A (en) | 1993-09-13 | 1998-11-10 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Adeno-associated viral (AAV) liposomes and methods related thereto |
US5656465A (en) | 1994-05-04 | 1997-08-12 | Therion Biologics Corporation | Methods of in vivo gene delivery |
US6406699B1 (en) | 1999-10-05 | 2002-06-18 | Gary W. Wood | Composition and method of cancer antigen immunotherapy |
ATE374244T1 (de) | 2000-02-11 | 2007-10-15 | Dana Farber Cancer Inst Inc | Identifizierung von antigenen peptiden durch zytotoxische t-lymphozyten aktiviert von dendritischen zellhybriden |
DE10232697A1 (de) | 2002-07-15 | 2004-02-05 | Universitätsklinikum Charité, Medizinische Fakultät der Humboldt-Universität zu Berlin | Verwendung von CD152 zur Behandlung von Autoimmunkrankheiten und Entzündungen |
DK1545204T3 (en) * | 2002-09-06 | 2016-11-14 | The Government Of The Us Secretary Dept Of Health And Human Services | Immunotherapy with in vitro selected antigen-specific lymphocytes following non-myeloablative lymphodepletive chemotherapy |
US20040250305A1 (en) | 2002-09-09 | 2004-12-09 | Latif Zuhair A. | Adoptive transfer and uses thereof |
AU2003300359A1 (en) | 2003-05-08 | 2004-12-13 | Xcyte Therapies, Inc. | Generation and isolation of antigen-specific t cells |
JPWO2007018198A1 (ja) | 2005-08-09 | 2009-02-19 | 国立大学法人 熊本大学 | Hla−a2陽性者用hsp105由来癌拒絶抗原ペプチド及びこれを含む医薬 |
US20080131415A1 (en) | 2006-11-30 | 2008-06-05 | Riddell Stanley R | Adoptive transfer of cd8 + t cell clones derived from central memory cells |
BRPI0812913B8 (pt) | 2007-06-18 | 2021-05-25 | Merck Sharp & Dohme | anticorpos monoclonais ou fragmento de anticorpo para o receptor de morte programada humano pd-1, polinucleotideo, método para produzir os referidos anticorpos ou fragmentos de anticorpos, composição que os compreende e uso dos mesmos |
CA2703947C (en) * | 2007-10-26 | 2018-12-04 | Governing Council Of The University Of Toronto | Therapeutic and diagnostic methods using tim-3 |
EP2245142B1 (en) * | 2008-01-29 | 2018-03-07 | Fred Hutchinson Cancer Research Center | Identification of cd8+ t cells that are cd161hi and/or il18r(alpha)hi and have rapid drug efflux capacity |
EP2247200B1 (en) | 2008-01-31 | 2020-11-25 | Bayer CropScience AG | The use of alternan as ingredient for certain foodstuffs |
CA2730050A1 (en) * | 2008-07-18 | 2010-01-21 | Sentoclone Ab | Composition comprising in vitro expanded t-lymphocytes and vessel formation inhibitors suitable in the treatment of cancer |
CN101625361A (zh) | 2009-02-26 | 2010-01-13 | 中国人民解放军第二军医大学 | 一种慢性乙型肝炎患者免疫状态的诊断方法 |
WO2012054792A2 (en) * | 2010-10-22 | 2012-04-26 | Virginia Commonwealth University | Composition and method for immunological treatment of cancer, prevention of cancer recurrence and metastasis, and overcoming immune suppressor cells |
US20120244133A1 (en) | 2011-03-22 | 2012-09-27 | The United States of America, as represented by the Secretary, Department of Health and | Methods of growing tumor infiltrating lymphocytes in gas-permeable containers |
CN102935228B (zh) * | 2011-08-15 | 2015-02-18 | 苏州丁孚靶点生物技术有限公司 | 用于肿瘤治疗的试剂、其用途及方法 |
JP2014020930A (ja) | 2012-07-18 | 2014-02-03 | Kanazawa Univ | 膵癌診断及び治療効果予測判定バイオマーカー |
EP2961416B1 (en) * | 2013-03-01 | 2019-11-13 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Methods of producing enriched populations of tumor reactive t cells from peripheral blood |
CN104371974B (zh) | 2014-10-24 | 2017-03-22 | 杭州阿诺生物医药科技股份有限公司 | 一种自体外周血淋巴细胞cik的培养方法 |
CN105754990A (zh) | 2016-01-29 | 2016-07-13 | 深圳精准医疗科技有限公司 | 一种pd-1/ctla-4双特异性抗体的制备方法及其应用 |
CR20200608A (es) | 2016-04-21 | 2021-01-20 | Immatics Biotechnologies Gmbh | INMUNOTERAPIA CONTRA EL MELANOMA Y OTROS TIPOS DE CÁNCER (Divisional 2018-0551) |
CN106177931B (zh) | 2016-08-25 | 2018-02-02 | 河北浓孚雨生物科技有限公司 | 免疫检测点双阻断ctl高效率杀伤细胞制剂的制备方法 |
CN106957905B (zh) | 2016-12-23 | 2020-12-04 | 孙涛 | 一种用于评估肿瘤免疫治疗效果的分子检测方法及引物组合物及试剂盒 |
JOP20190224A1 (ar) | 2017-03-29 | 2019-09-26 | Iovance Biotherapeutics Inc | عمليات من أجل إنتاج الخلايا اللمفاوية المرتشحة للأورام واستخداماتها في العلاج المناعي |
RU2662916C1 (ru) | 2017-06-05 | 2018-07-31 | Общество с ограниченной ответственностью "Альтернативные Инновационные Технологии" | Способ терапии метастатического рака с использованием вируса Сендай |
US20200116700A1 (en) | 2017-06-30 | 2020-04-16 | Osaka University | Method for predicting effect of tumor immunotherapy using tumor cytotoxic activity of peripheral blood t cells as index |
CN108254557B (zh) | 2017-12-26 | 2019-05-31 | 首都医科大学附属北京地坛医院 | 用cd8阳性的t细胞上pd-1和tigit确定hbv相关原发性肝癌预后的系统 |
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