JP2015519080A - 養子細胞療法のための改良型細胞培養方法 - Google Patents
養子細胞療法のための改良型細胞培養方法 Download PDFInfo
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Abstract
Description
本出願は、2009年12月8日に出願された「養子細胞療法のための改良型細胞培養方法」という名称の米国仮出願第61/267761号の利点を請求する2010年12月8日に出願された「養子細胞療法のための改良型細胞培養方法」という名称の米国特許出願第12/963597号(以下、「親出願」)(その全体を参照により本出願に援用する)の一部継続出願である。
抗原提示細胞(APC):特定の抗原に応答するように目的細胞を惹起するために作用する細胞。
CTL:細胞傷害性T細胞。
目的細胞:生産プロセスにおいて量を増やすことを目標とする特異的な型の細胞。一般に、目的細胞は非接着性であり、例としては制御性T細胞(Treg)、ナチュラルキラー細胞(NK)、腫瘍浸潤性リンパ球(TIL)、初代Tリンパ球及び多様な抗原特異的細胞、及び他の多くのもの(これらはすべて、機能、生体内での残留性又は安全性を改良するように遺伝子改変することもできる)が挙げられる。臨床的使用に必要な細胞は、フィーダー細胞及び/又は抗原提示細胞を用いて増殖させることができるが、これらの細胞としては、PBMC、PHA blast、OKT3 T、B blast、LCL及びK562(天然又は発現するように遺伝子改変されており、抗原及び/又はエピトープ、並びに41BBL、OX40、CD80、CD86、HLA及びその他多くのものなどの共刺激分子)を挙げることができ、これらはペプチド又は他の関連する抗原でパルスする場合もあれば、しない場合もある。
EBV:エプスタイン・バーウイルス。
EBV−CTL:EBV感染細胞又はEBV由来のペプチドを発現したり提示したりする細胞を、T細胞表面受容体により特異的に認識したT細胞。
EBV−LCL:エプスタイン・バーウイルスで形質転換されたBリンパ芽球様細胞系。
フィーダー細胞:目的細胞の量を増大させるように作用する細胞。状況によっては抗原提示細胞もフィーダー細胞として作用することができる。
生育面:細胞がその上に静置される、培養器具内の領域。
PBMC:末梢血由来の末梢血単核細胞で、いくつかの目的細胞の源となり、フィーダー細胞として作用することができる。
応答細胞(R):刺激細胞に反応する細胞。
静置細胞培養:常套的な操作のために培養器具の設定場所が移動される場合、及び/又は細胞に新鮮培地などが定期的に供給される場合以外は、撹拌されたり混合されたりしない培地中で細胞を培養する方法。一般に、静置培養中の培地は、通常、静止状態にある。本発明は静置細胞培養方法に関する。
刺激:抗原提示及び/又はフィーダー細胞が目的細胞上で有する作用。
刺激細胞(S):応答細胞に影響を及ぼす細胞。
表面密度:細胞が静置される器具内の表面の、単位面積当たりの細胞量。
細胞表面:Becton−Dickinson(アメリカ合衆国カリフォルニア州マウンテンビュー)からのフィコエリトリン(PE)、フルオレセインイソチオシアネート(FITC)、ペリオディン(periodin)クロロフィルタンパク質(PerCP)及びCD3、CD4、CD8、CD56、CD16、CD62L、CD45RO、CD45RA、CD27、CD28、CD25、CD44に対するアロフィコシアニン(APC)結合モノクローナル抗体(MAb)で細胞を染色した。PE結合四量体(Baylor College of Medicine)及びAPC結合五量体(イギリス、オックスフォードのProimmune Ltd社)を使用してEBV−CTL前駆体の頻度を定量化した。細胞表面及び五量体染色のための、10000及び100000のライブイベントをFACSCaliburフローサイトメーターでそれぞれ獲得し、Cell Questソフトフェア(Becton Dickinson)を用いてデータを分析した。
a.目的細胞は、抗原提示細胞及び/又はフィーダー細胞の存在下、生育面が気体透過性材料からなるものではない場合には最大で1ml/cm2の培地容量:表面積比であり、生育面が気体透過性材料からなる場合には最大で2ml/cm2の培地容量:表面積比であり、
b.生産サイクル開始時の好ましい表面密度条件は、標的細胞表面密度が好ましくは0.5×106個/cm2未満であり、より好ましくは図4に記載されるように低下しており、
c.目的細胞の表面密度+抗原提示細胞及び/又はフィーダー細胞の表面密度は、好ましくは少なくとも約1.25×105個/cm2である。
a.抗原提示細胞及び/又はフィーダー細胞の存在下で、少なくとも2ml/cm2の培地容量:表面積比で、気体透過性材料からなる生育面面積上に目的細胞を播種すること、
b.標的細胞表面密度が約0.5×106個/cm2の従来密度以内になるような好ましい表面密度条件を生産サイクル開始時に確立すること、
c.従来の表面密度約2×106個/cm2を超えて目的細胞群が増殖することができるようにすること、及び
d.より多くの目的細胞が求められる場合には、気体透過性材料からなる追加の生育面に目的細胞を再分配し、十分な目的細胞が得られるまで工程a〜dを繰り返すこと。
a.抗原提示細胞及び/又はフィーダー細胞の存在下で、少なくとも2ml/cm2の培地容量:表面積比で、気体透過性材料からなる生育面面積上に目的細胞を播種すること、
b.標的細胞表面密度が従来の密度未満、好ましくは目的細胞約0.5×106個/cm2〜約3900個/cm2の範囲内であり、かつ、目的細胞及び抗原提示細胞及び/又はフィーダー細胞の合計が少なくとも約1.25×105個/cm2であるような好ましい表面密度条件を生産サイクル開始時に確立すること、
c.約2×106個/cm2の従来の表面密度を超えて目的細胞群が増殖することを可能にすること、
d.より多くの目的細胞が求められる場合には、気体透過性材料からなる追加の生育面に目的細胞を再分配し、十分な目的細胞が得られるまで工程a〜dを繰り返すこと。
a)レトロウイルス、アデノウイルス、アデノ関連ウイルス又はレンチウイルスなどのウイルスベクターでの遺伝的修飾、及び/又は
b)トランスポゾン及びトランスポーゼース(例えば、Sleeping Beauty)を使用するエレクトロポレーション及び/又はリポフェクション法、及び/又はピギーバック(Piggybac)技術などの物理的及び/又は化学的技術により組み込まれるDNA及び/又はRNAベクターの使用を含む、非ウイルスベクターによる遺伝的修飾、及び/又は
c)Tビヒクル移動を改変する、自殺遺伝子を組み込む、レシピエントの免疫再構築(例えば、サイトカイン生産)を改善する、及び/又は直接的な抗ウイルス又は抗腫瘍効果を導く(例えば、キメラ抗原受容体)又は自己免疫疾患治療のために免疫応答を抑制する1以上のトランスジーンを包含させるための遺伝的修飾、及び/又は
d)Tビヒクルの移動を改善するCCR1、CCR2、CCR3、CCR4、CCR5、CCR6、CCR7、CCR8、CCR9、CCR10、CXCR1、CXCR2、CXCR3−A、CXCR5、CXCR6、CX3CR1及び/又はXCR1などの1以上のケモカイン受容体の発現によりTビヒクルの移動を改善するための遺伝的修飾、及び/又は
e)GM−CSF、TNFα、INFγ、IL2、IL8、IL15、IL7、IL12、IL21又はIL26などの1以上のサイトカインのTビヒクル発現により、又は、共刺激分子CD80、CD86、41BBL、OX40Lの発現又は過剰発現により、レシピエントの免疫再構築を改善するための遺伝的修飾、及び/又は
f)チミジンキナーゼTK遺伝子、CD20、CD19、iカスパーゼ9などの1以上の自殺遺伝子の発現によりTビヒクルの死を誘導するための遺伝的修飾、及び/又は
g)i)IgG−FC領域由来のCH2CH3配列を使用する細胞外スペーサーと、又はii)CD28、CD4、CD3又はCD8の配列を含むがこれらに限定されない膜貫通成分と、iii)CD3(エンドドメイン(endodomain)と連結された、又はiv)CD3(エンドドメインをコードするサイトカイン受容体又はサイトカインなどの天然リガンドの発現により連結された特定の抗体から単離された単鎖可変断片(scFv)を介して腫瘍標的を認識するキメラ抗原受容体(CAR)などの1以上のトランスジーンの発現、を含むがこれらに限定されない、直接的な抗ウイルス又は抗腫瘍効果を導くための遺伝的修飾、及び/又は
h)例えば、IL4、IL6、IL10、IL13、TFGβなどの1以上の免疫抑制サイトカインを生産するトランスジーンの発現により又はCTLA−4、PD1などの競合リガンドの発現により、自己免疫疾患治療のために免疫応答を抑制するための遺伝的修飾。
a)DNA、RNA、組換えタンパク質、ペプチド又はアプタマーを担持するための生物学的ビヒクルとして、
b)化学化合物を担持するための生物学的ビヒクルとして、
c)化学療法剤、小分子、ナノ粒子、ホルモン作動薬又は拮抗薬、抗ウイルス剤、抗真菌剤、抗寄生虫剤を含むがこれらに限定されない治療目的を有する化学化合物の担持を許容する生物学的ビヒクルとして、及び/又は
d)治療目的は持たないが、転移性疾患部位の同定を可能にする生体内での同定及び画像化を含むがこれらに限定されない副次的利点を有する1以上の化学化合物を担持するための生物学的ビヒクルとして。
Claims (15)
- 目的の天然抗原特異性を有するT細胞群を作成するための方法であって、
A.細胞培養器具内にPBMC又は臍帯血を添加する過程と、
B.細胞培養器具内に培地及び2つ以上の抗原を添加し、2つ以上の抗原特異的T細胞群の成長を活性化する過程であって、各抗原特異的T細胞群が前記抗原の1つに対する天然抗原特異性を有する過程と、
C.少なくとも1つの抗原特異的T細胞群が前記抗原の少なくとも1つに応答して個体数増殖を開始するための期間を許容する過程と、
D.少なくとも1つの抗原特異的T細胞群の存在及び/又は量を決定するべく培養物を評価する過程と、
E.いずれの抗原特異的T細胞群が継続増殖に適するのかを決定する過程と、
F.継続増殖に適すると認められた1つ又は複数の抗原特異的T細胞群によってのみ認識される抗原で培養物を再刺激する過程と、
を含むことを特徴とする方法。 - 請求項1の方法であって、プロセスの結果が単一の抗原特異的T細胞群を作成することを特徴とする方法。
- 請求項1の方法であって、継続増殖に適する前記1つ又は複数の抗原特異的T細胞群が、正常な細胞上には存在しない抗原のみを認識することができる天然抗原特異性を包含することを特徴とする方法。
- 請求項1の方法であって、継続増殖に適する前記1つ又は複数の抗原特異的T細胞群が、正常なヒト細胞上には存在しない抗原のみを認識することができる天然抗原特異性を包含することを特徴とする方法。
- 請求項4の方法であって、継続増殖に適する前記1つ又は複数の抗原特異的T細胞群が、正常なヒト細胞上には存在しない抗原の単一エピトープのみを認識することができる天然抗原特異性を包含することを特徴とする方法。
- 請求項3の方法であって、継続増殖に適する1つ又は複数の抗原特異的T細胞群が正常な細胞上には存在しない抗原のみを認識することができる天然抗原特異性を包含し、爬虫類、両生類、魚類、鳥類、無脊椎動物、細菌類、真菌類、寄生虫、海綿動物及び/又はウイルスの抗原を含む抗原を認識することができることを特徴とする方法。
- 請求項1の方法であって、細胞培養器具が気体透過性材料を包含することを特徴とする方法。
- 請求項7の方法であって、PBMC又は臍帯血が気体透過性材料上に存在することを特徴とする方法。
- 請求項1の方法であって、培地の最低高さと最高高さとの距離が2.0cmを超えることを特徴とする方法。
- 請求項1の方法であって、PBMC又は臍帯血が500000cm2未満の表面密度で存在することを特徴とする方法。
- 目的の天然抗原特異性を有するT細胞群を作成するための方法であって、
A.細胞培養器具内にPBMC又は臍帯血を添加する過程と、
B.細胞培養器具内に培地及び抗原を添加し、前記抗原に対する天然抗原特異性を有する抗原特異的T細胞の成長を活性化する過程と、を含み
C.培地の最低高さと最高高さとの距離が2.0cmを超え、
D.PBMC又は臍帯血が気体透過性材料上に存在し、
E.前記天然抗原特異性が正常な細胞上には存在しない抗原のみを認識することができることを特徴とする方法。 - 請求項11の方法であって、抗原特異的T細胞が正常なヒト細胞上には存在しない抗原のみを認識することができる天然抗原特異性を有することを特徴とする方法。
- 請求項12の方法であって、抗原特異的T細胞が正常なヒト細胞上には存在しない抗原の単一エピトープのみを認識することができる天然抗原特異性を有することを特徴とする方法。
- 請求項12の方法であって、抗原特異的T細胞が正常な細胞上には存在しない抗原のみを認識することができる天然抗原特異性を有し、少なくとも爬虫類、両生類、魚類、鳥類、無脊椎動物、細菌類、真菌類、寄生虫、海綿動物又はウイルスの抗原を含む抗原を認識することができることを特徴とする方法。
- 請求項11の方法であって、PBMC又は臍帯血が1cm2当たり細胞500000個未満の表面密度で存在することを特徴とする方法。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018138059A (ja) * | 2012-06-11 | 2018-09-06 | ウィルソン ウォルフ マニュファクチャリング コーポレイションWilson Wolf Manufacturing Corporation | 養子細胞療法のための改良型細胞培養方法 |
Families Citing this family (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8956860B2 (en) | 2009-12-08 | 2015-02-17 | Juan F. Vera | Methods of cell culture for adoptive cell therapy |
AU2013204922B2 (en) | 2012-12-20 | 2015-05-14 | Celgene Corporation | Chimeric antigen receptors |
US10238690B2 (en) | 2013-03-15 | 2019-03-26 | Celgene Corporation | Modified T lymphocytes comprising an inducible caspase and methods of apoptosis |
WO2015157636A1 (en) | 2014-04-10 | 2015-10-15 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy |
NZ729046A (en) * | 2014-08-12 | 2022-07-29 | Celgene Corp | Car-t lymphocytes engineered to home to lymph node b cell zone, skin, or gastrointestinal tract |
CN106755023A (zh) * | 2015-10-15 | 2017-05-31 | 中国人民解放军军事医学科学院附属医院 | 带安全开关的嵌合抗原受体免疫细胞及其制备方法与应用 |
GB201522097D0 (en) | 2015-12-15 | 2016-01-27 | Cellular Therapeutics Ltd | Cells |
CA3030156A1 (en) | 2016-07-07 | 2018-01-11 | Iovance Biotherapeutics, Inc. | Programmed death 1 ligand 1 (pd-l1) binding proteins and methods of use thereof |
CN106119193B (zh) * | 2016-07-28 | 2019-10-29 | 上海闪锦生物科技有限公司 | 一种兼有nk细胞特质的抗原特异性t细胞的制备方法 |
BR112019008305A2 (pt) | 2016-10-26 | 2019-08-06 | Iovance Biotherapeutics Inc | métodos para expansão de linfócitos infiltrantes de tumor, para avaliação da atividade metabólica de uma população de células til, para tratamento de um sujeito com câncer e para ensaiar tils, e, população de tils expandidos |
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 |
CA3044250A1 (en) | 2016-11-17 | 2018-05-24 | Iovance Biotherapeutics, Inc. | Remnant tumor infiltrating lymphocytes and methods of preparing and using the same |
EP3565586A1 (en) | 2017-01-06 | 2019-11-13 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes with potassium channel agonists and therapeutic uses thereof |
KR20190104048A (ko) | 2017-01-06 | 2019-09-05 | 이오반스 바이오테라퓨틱스, 인크. | 종양 괴사 인자 수용체 슈퍼패밀리 (tnfrsf) 효능제를 사용한 종양 침윤 림프구 (til)의 확장 및 til과 tnfrsf 효능제의 치료 조합물 |
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 |
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 |
WO2018209115A1 (en) | 2017-05-10 | 2018-11-15 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof |
WO2019103857A1 (en) | 2017-11-22 | 2019-05-31 | Iovance Biotherapeutics, Inc. | Expansion of peripheral blood lymphocytes (pbls) from peripheral blood |
AR112072A1 (es) | 2017-06-05 | 2019-09-18 | Iovance Biotherapeutics Inc | Métodos de uso de linfocitos infiltrantes de tumor en melanoma doble refractario |
SG11202004457XA (en) | 2017-11-17 | 2020-06-29 | Iovance Biotherapeutics Inc | Til expansion from fine needle aspirates and small biopsies |
JP2021508104A (ja) | 2017-12-15 | 2021-02-25 | 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 | 腫瘍浸潤リンパ球の有益な投与を決定するシステム及び方法並びにその使用方法、並びに腫瘍浸潤リンパ球の有益な投与及びその使用方法 |
WO2019136459A1 (en) | 2018-01-08 | 2019-07-11 | Iovance Biotherapeutics, Inc. | Processes for generating til products enriched for tumor antigen-specific t-cells |
EP3737743A1 (en) | 2018-01-08 | 2020-11-18 | Iovance Biotherapeutics, Inc. | Processes for generating til products enriched for tumor antigen-specific t-cells |
US11713446B2 (en) | 2018-01-08 | 2023-08-01 | Iovance Biotherapeutics, Inc. | Processes for generating TIL products enriched for tumor antigen-specific T-cells |
CA3094957A1 (en) | 2018-03-29 | 2019-10-03 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy |
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 |
WO2019217753A1 (en) | 2018-05-10 | 2019-11-14 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy |
TW202031273A (zh) | 2018-08-31 | 2020-09-01 | 美商艾歐凡斯生物治療公司 | 抗pd-1抗體難治療性之非小細胞肺癌(nsclc)病患的治療 |
SG11202101787XA (en) | 2018-09-20 | 2021-04-29 | Iovance Biotherapeutics Inc | Expansion of tils from cryopreserved tumor samples |
AU2019374761A1 (en) | 2018-11-05 | 2021-06-10 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes and uses of the same in immunotherapy |
US20230039976A1 (en) | 2018-11-05 | 2023-02-09 | Iovance Biotherapeutics, Inc. | Selection of improved tumor reactive t-cells |
BR112021008549A2 (pt) | 2018-11-05 | 2022-01-04 | Iovance Biotherapeutics Inc | Método de tratamento de carcinoma pulmonar de células não pequenas com uma população de linfócitos infiltrantes de tumor |
US20220033775A1 (en) | 2018-11-05 | 2022-02-03 | Iovance Biotherapeutics, Inc. | Expansion of tils utilizing akt pathways inhibitors |
EP3898949A1 (en) | 2018-12-19 | 2021-10-27 | Iovance Biotherapeutics, Inc. | Methods of expanding tumor infiltrating lymphocytes using engineered cytokine receptor pairs and uses thereof |
WO2020232029A1 (en) | 2019-05-13 | 2020-11-19 | Iovance Biotherapeutics, Inc. | Methods and compositions for selecting tumor infiltrating lymphocytes and uses of the same in immunotherapy |
CA3155727A1 (en) | 2019-10-25 | 2021-04-29 | Cecile Chartier-Courtaud | Gene editing of tumor infiltrating lymphocytes and uses of same in immunotherapy |
EP4073236A1 (en) | 2019-12-11 | 2022-10-19 | Iovance Biotherapeutics, Inc. | Processes for the production of tumor infiltrating lymphocytes (tils) and methods of using the same |
WO2021123832A1 (en) | 2019-12-20 | 2021-06-24 | Instil Bio (Uk) Limited | Devices and methods for isolating tumor infiltrating lymphocytes and uses thereof |
EP4139440A1 (en) | 2020-04-22 | 2023-03-01 | Iovance Biotherapeutics, Inc. | Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy |
JP2023524108A (ja) | 2020-05-04 | 2023-06-08 | 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 | 改良された腫瘍反応性t細胞の選択 |
EP4146794A1 (en) | 2020-05-04 | 2023-03-15 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes and uses of the same in immunotherapy |
JP2023546359A (ja) | 2020-10-06 | 2023-11-02 | 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 | 腫瘍浸潤リンパ球療法によるnsclc患者の治療 |
WO2022076606A1 (en) | 2020-10-06 | 2022-04-14 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
CA3201818A1 (en) | 2020-12-11 | 2022-06-16 | Maria Fardis | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with braf inhibitors and/or mek inhibitors |
US20240123067A1 (en) | 2020-12-17 | 2024-04-18 | Iovance Biotherapeutics, Inc. | Treatment of cancers with tumor infiltrating lymphocyte therapies |
AU2021401302A1 (en) | 2020-12-17 | 2023-07-06 | Iovance Biotherapeutics, Inc. | Treatment with tumor infiltrating lymphocyte therapies in combination with ctla-4 and pd-1 inhibitors |
BR112023021665A2 (pt) | 2021-04-19 | 2023-12-19 | Iovance Biotherapeutics Inc | Método para tratar um câncer, e, composição |
CA3226942A1 (en) | 2021-07-28 | 2023-02-02 | Iovance Biotherapeutics, Inc. | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with kras inhibitors |
CA3235824A1 (en) | 2021-10-27 | 2023-05-04 | Frederick G. Vogt | Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy |
WO2023086803A1 (en) | 2021-11-10 | 2023-05-19 | Iovance Biotherapeutics, Inc. | Methods of expansion treatment utilizing cd8 tumor infiltrating lymphocytes |
WO2023147486A1 (en) | 2022-01-28 | 2023-08-03 | Iovance Biotherapeutics, Inc. | Tumor infiltrating lymphocytes engineered to express payloads |
WO2024030758A1 (en) | 2022-08-01 | 2024-02-08 | Iovance Biotherapeutics, Inc. | Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009213462A (ja) * | 2008-02-15 | 2009-09-24 | Kist-Europe Forschungs Gmbh | 細胞改変方法および細胞改変装置 |
WO2012138858A1 (en) * | 2011-04-08 | 2012-10-11 | Baylor College Of Medicine | Reversing the effects of the tumor microenvironment using chimeric cytokine receptors |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5731160A (en) * | 1992-05-26 | 1998-03-24 | Rijksuniversiteit Leiden | Induction of antigen specific T-lymphocyte responses by stimulation with peptide loaded MHC class I molecules on antigen processing defective mammalian cell lines |
US20030235908A1 (en) * | 2000-02-24 | 2003-12-25 | Xcyte Therapies, Inc. | Activation and expansion of cells |
WO2003057171A2 (en) * | 2002-01-03 | 2003-07-17 | The Trustees Of The University Of Pennsylvania | Activation and expansion of t-cells using an engineered multivalent signaling platform |
US7745140B2 (en) * | 2002-01-03 | 2010-06-29 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an engineered multivalent signaling platform as a research tool |
JP2006524991A (ja) * | 2003-05-08 | 2006-11-09 | エクサイト セラピーズ インコーポレーティッド | 抗原特異的t細胞の作製および単離の方法 |
ES2672895T3 (es) * | 2005-08-05 | 2018-06-18 | Helmholtz Zentrum München Deutsches Forschungszentrum Für Gesundheit Und Umwelt Gmbh | Generación de células T específicas de antígeno |
SG178885A1 (en) * | 2009-08-24 | 2012-04-27 | Baylor College Medicine | Generation of ctl lines with specificity against multiple tumor antigens or multiple viruses |
SG181559A1 (en) * | 2009-12-08 | 2012-07-30 | Wolf Wilson Mfg Corp | Improved methods of cell culture for adoptive cell therapy |
US20130115617A1 (en) * | 2009-12-08 | 2013-05-09 | John R. Wilson | Methods of cell culture for adoptive cell therapy |
CN103930130B (zh) * | 2011-09-08 | 2016-07-06 | 耶达研究及发展有限公司 | 抗第三方中央型记忆t细胞、其产生方法以及其在移植和疾病治疗中的应用 |
AU2012351347B2 (en) * | 2011-12-12 | 2016-05-19 | Baylor College Of Medicine | Process of expanding T cells |
GB201121308D0 (en) * | 2011-12-12 | 2012-01-25 | Cell Medica Ltd | Process |
PT3591047T (pt) * | 2012-02-09 | 2022-10-20 | Baylor College Medicine | Pepmixes para gerar ctls multivirais com larga especifidade |
US20130217122A1 (en) * | 2012-02-21 | 2013-08-22 | The Trustees Of The University Of Pennsylvania | Expansion of Interferon-Gamma-Producing T-Cells Using Glypican-3 Peptide Library |
CN102719399A (zh) * | 2012-04-28 | 2012-10-10 | 北京爱根生物科技有限公司 | 自体特异性t细胞的体外扩增方法及所制备的t细胞体系、体系的药物应用和组分监测方法 |
JP6386447B2 (ja) * | 2012-05-18 | 2018-09-05 | ウィルソン ウォルフ マニュファクチャリング コーポレイションWilson Wolf Manufacturing Corporation | 養子細胞療法のための改良された細胞培養法 |
IL302514A (en) * | 2012-06-11 | 2023-07-01 | Wilson Wolf Mfg Corporation | Improved cell culture methods for stress cell therapy |
US10584354B2 (en) * | 2013-09-23 | 2020-03-10 | Wilson Wolf Manufacturing | Methods of genetically modifying animal cells |
AU2017330379B2 (en) * | 2016-09-23 | 2023-07-13 | Memorial Sloan Kettering Cancer Center | Generation and use in adoptive immunotherapy of stem cell-like memory T cells |
TW201814042A (zh) * | 2016-09-26 | 2018-04-16 | 新加坡商泰莎治療私人有限公司 | T細胞擴展方法 |
EP3652306A1 (en) * | 2017-07-13 | 2020-05-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for increasing expansion and immunosuppressive capacity of a population of cd8+cd45rclow/-tregs |
CA3149145A1 (en) * | 2019-07-29 | 2021-02-04 | Baylor College Of Medicine | Antigen-specific t cell banks and methods of making and using the same therapeutically |
MX2022001967A (es) * | 2019-08-16 | 2022-05-16 | Baylor College Medicine | Composiciones de células t específicas para virus de terceros y métodos para prepararlas y usarlas en profilaxis antiviral. |
US20210371822A1 (en) * | 2020-05-27 | 2021-12-02 | University Of Southern California | Methods for expanding sars-cov2-antigen-specific t cells, compositions and uses related thereto |
-
2013
- 2013-06-11 IL IL302514A patent/IL302514A/en unknown
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- 2014-11-17 IL IL235739A patent/IL235739B/en active IP Right Grant
-
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- 2018-06-15 JP JP2018114352A patent/JP2018138059A/ja active Pending
-
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- 2019-10-03 AU AU2019240684A patent/AU2019240684A1/en not_active Abandoned
-
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- 2020-03-31 IL IL273719A patent/IL273719B/en unknown
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-
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-
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009213462A (ja) * | 2008-02-15 | 2009-09-24 | Kist-Europe Forschungs Gmbh | 細胞改変方法および細胞改変装置 |
WO2012138858A1 (en) * | 2011-04-08 | 2012-10-11 | Baylor College Of Medicine | Reversing the effects of the tumor microenvironment using chimeric cytokine receptors |
Non-Patent Citations (5)
Title |
---|
NAKAZAWA Y. ET AL., MOLECULAR THERAPY, vol. 19(12)(2011), JPN6017009780, pages 2133 - 2143, ISSN: 0003521740 * |
VALLERA D.A., CANCER RES., vol. 60(2000), JPN6017009781, pages 976 - 984, ISSN: 0003521743 * |
VERA J.F. ET AL.: "Safely Improving the in Vivo survival of Tumor Specific Cytotoxic T Lymphocytes by Co-Transfer of IL", BLOOD, vol. 112(11)(2008), JPN6017009783, pages 3534, ISSN: 0003521741 * |
ZOHREN F. ET AL.: "Genetic Modification of Multi Leukemia Antigen-Specific Cytotoxic T Lymphocytes(CTL) to Enhance In V", BLOOD, vol. 118(21)(2011), JPN6017009784, pages 644, ISSN: 0003521742 * |
大沢 利昭 他, 免疫学辞典, vol. 第2版, JPN6018005080, 2001, pages 634, ISSN: 0003739992 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018138059A (ja) * | 2012-06-11 | 2018-09-06 | ウィルソン ウォルフ マニュファクチャリング コーポレイションWilson Wolf Manufacturing Corporation | 養子細胞療法のための改良型細胞培養方法 |
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CN104411819A (zh) | 2015-03-11 |
WO2013188427A1 (en) | 2013-12-19 |
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IL235739B (en) | 2020-04-30 |
SG10201610387QA (en) | 2017-02-27 |
EP2859093A1 (en) | 2015-04-15 |
IL235739A0 (en) | 2015-01-29 |
AU2022202172A1 (en) | 2022-04-21 |
IL302514A (en) | 2023-07-01 |
AU2013274416B2 (en) | 2019-07-04 |
JP7244461B2 (ja) | 2023-03-22 |
CN104411819B (zh) | 2019-05-10 |
AU2019240684A1 (en) | 2019-10-24 |
IL288241B1 (en) | 2023-06-01 |
CA2873608A1 (en) | 2013-12-19 |
EP2859093A4 (en) | 2016-08-17 |
JP2023065668A (ja) | 2023-05-12 |
CN110241086A (zh) | 2019-09-17 |
JP2018138059A (ja) | 2018-09-06 |
IL273719A (en) | 2020-05-31 |
SG11201407819UA (en) | 2014-12-30 |
JP2020174685A (ja) | 2020-10-29 |
IL288241A (en) | 2022-01-01 |
AU2013274416A1 (en) | 2015-01-15 |
IL288241B2 (en) | 2023-10-01 |
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