JP4929174B2 - リンパ球の製造方法 - Google Patents
リンパ球の製造方法 Download PDFInfo
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- JP4929174B2 JP4929174B2 JP2007530976A JP2007530976A JP4929174B2 JP 4929174 B2 JP4929174 B2 JP 4929174B2 JP 2007530976 A JP2007530976 A JP 2007530976A JP 2007530976 A JP2007530976 A JP 2007530976A JP 4929174 B2 JP4929174 B2 JP 4929174B2
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Description
Greenberg P.D.著,1992年発行,Advances in Immunology Reusser P.他3名,Blood,1991年,Vol.78,No.5,P1373〜1380 Riddell S.A.他4名,J.Immunol.,1991年,Vol.146,No.8,P2795〜2804 Riddell S.R.他1名,J.Immunol.Methods,1990年,Vol.128,No.2,P189〜201 Rosenberg S.A.他,N.Engl.J.Med.,1987年,Vol.316,No.15,P889〜897 Rosenberg S.A.他,N.Engl.J.Med.,1988年,Vol.319,No.25,P1676〜1680 Ho M.他9名,Blood,1993年,Vol.81,No.8,P2093〜2101 Koberda J.他2名,J.Cancer Res.Clin.Oncol.,1993年,Vol.119,No.3,P131−136 Deane F.Momer著,1988年発行,FIBRONECTIN,ACADEMIC PRESS INC.,P1〜24 Kimizuka F.他8名,J.Biochem.,1991年,Vol.110,No.2,p284−291 Hanenberg H.他5名,Human Gene Therapy,1997年,Vol.8,No.18,p2193−2206
本明細書中に記載のフィブロネクチンおよびそのフラグメントは、天然から得られたもの、または人為的に合成されたもののいずれでもよい。フィブロネクチンおよびそのフラグメントは、例えば、ルオスラーティ E.ら〔Ruoslahti E.,et al.、ジャーナル・オブ・バイオロジカル・ケミストリー(J.Biol.Chem.)、第256巻、第14号、第7277〜7281頁(1981)〕の開示に基づき、天然起源の物質から実質的に純粋な形態で製造することができる。ここで、本明細書に記載された実質的に純粋なフィブロネクチンまたはフィブロネクチンフラグメントとは、これらが天然においてフィブロネクチンと一緒に存在する他のタンパク質を本質的に含有していないことを意味する。上記のフィブロネクチンおよびそのフラグメントは、それぞれ単独で、もしくは複数の種類のものを混合して本発明に使用することができる。
1、Escherichia coli HB101/pHD101
FERM BP−2264(H−271をコードするプラスミドを保有する大腸菌;寄託日 1989年1月30日)、
2、Escherichia coli HB101/pCH102
FERM BP−2800(CH−296をコードするプラスミドを保有する大腸菌;寄託日 1989年5月12日)、
3、Escherichia coli HB101/pCH101
FERM BP−2799(CH−271をコードするプラスミドを保有する大腸菌;寄託日 1989年5月12日)、
4、Escherichia coli HB101/pHD102
FERM BP−7420(H−296をコードするプラスミドを保有する大腸菌;寄託日 1989年5月12日)、
5、Escherichia coli JM109/pTF7221
FERM BP−1915(C−274をコードするプラスミドを保有する大腸菌;寄託日 1988年6月17日)、
6、Escherichia coli HB101/pCS25
FERM BP−5723(C−CS1をコードするプラスミドを保有する大腸菌;寄託日 1990年3月5日)、
7、pCold14−CH296Na
FERM BP−10073(CH−296Naをコードするプラスミド;寄託日 2004年7月23日)
8、Escherichia coli HB101/pCHV89
FERM P−12182(CHV−89をコードするプラスミドを保有する大腸菌;寄託日 1991年4月8日)、
9、Escherichia coli HB101/pCHV179
FERM P−12183(CHV−179をコードするプラスミドを保有する大腸菌;寄託日 1991年4月8日)。
以下、本発明のリンパ球の製造方法について具体的に説明する。本発明の方法は、(a)前述のフィブロネクチン、そのフラグメントまたはそれらの混合物、(b)CD3リガンド、及び(c)CD28リガンドの存在下にリンパ球の拡大培養を行なう工程を包含することを特徴とする、リンパ球の製造方法である。以下、上記の(a)前述のフィブロネクチン、そのフラグメントまたはそれらの混合物、(b)CD3リガンド、及び(c)CD28リガンドを本発明の有効成分と称することがある。
(A)CD44に結合活性を有する物質
(B)CD44リガンドがCD44に結合することにより発せられるシグナルを制御し得る物質
(C)成長因子の成長因子レセプターへの結合を阻害し得る物質
(D)成長因子が成長因子レセプターに結合することにより発せられるシグナルを制御し得る物質
(X)使用する細胞培養用器材における培養面積に対する細胞量の比率が、好適には1cell/cm2〜5×105cells/cm2、より好適には10cells/cm2〜1×105cells/cm2、さらに好適には1×102cells/cm2〜5×104cells/cm2である。
(Y)培地中の細胞の濃度が、好適には1cell/mL〜5×105cells/mL、より好適には10cells/mL〜1×105cells/mL、さらに好適には1×102cells/mL〜5×104cells/mLである。
なお、ここで細胞量とは、培養に使用する細胞の個数をいう。
(1)PBMCの分離と保存
インフォームド・コンセントの得られたヒト健常人ドナーより成分採血を実施後、採血液をリン酸緩衝生理食塩水で2倍希釈し、Ficol−paque(AmershamBiosciences社製)上に重層して500×gで20分間遠心分離した。中間層の末梢血単核球細胞(PBMC)をピペットで回収、洗浄した。採取したPBMCは90%FBS(Cambrex社製)/10%DMSO(SIGMA社製)からなる保存液に懸濁し、液体窒素中にて保存した。リンパ球拡大培養時にはこれら保存PBMCを37℃水浴中にて急速溶解し、10μg/mL DNase(Calbiochem社製)を含むRPMI1640培地(SIGMA社製)で洗浄後、トリパンブルー染色法にて生細胞数を算出して各実験に供した。
12穴細胞培養プレート(ベクトン・ディッキンソン社製)に終濃度5μg/mLの抗ヒトCD3抗体(ヤンセン協和社製)を含む酢酸緩衝水溶液を1.9mLずつ添加した。酢酸緩衝水溶液は、0.2M酢酸(ナカライテスク社製、00212−43より調製)と0.2M酢酸ナトリウム水溶液(ナカライテスク社製、311−19より調製)を1:4の比率(容量比)で混合し、pHが5.3になるように調製した。この時、抗ヒトCD28抗体による刺激が行われる群には抗ヒトCD28抗体(DakoCytomation社製、RB342)を終濃度5μg/mLとなるように、CH−296による刺激が行われる群にはCH−296を終濃度25μg/mLとなるように添加した。これらのプレートは室温で5時間インキュベートした後、抗体、CH−296を含む酢酸緩衝水溶液を吸引除去し、各ウェルをリン酸緩衝生理食塩水で2回、RPMI培地で1回洗浄し、各実験に供した。
3%humanAB血清(Cambrex社製)を含むAIM−V(Invitrogen社製、以下3%AIM−Vと略す)に0.5×106cells/mLとなるように実施例1−(1)で調製したPBMCを懸濁し細胞液を調整後、実施例1−(2)で調製した抗体及びCH−296固定化プレートに3%AIM−Vを2mL/ウェルで添加し、そこへ調整した細胞液を1mL/ウェルずつ加えた。その後、抗ヒトCD3抗体単一刺激群および抗ヒトCD3抗体とCH−296共刺激群には終濃度1000U/mLとなるようにIL−2(塩野義製薬社製)を添加し(すなわち抗ヒトCD28抗体を用いて刺激を行った群にはIL−2を添加しない)、これらのプレートを5%CO2中37℃で培養した(培養0日目)。各群について、培養開始後4日目、7日目、11日目には、以下の方法で継代培養操作を行った。細胞培養液を一部回収し、トリパンブルー染色法にて生細胞数を計測後、1%humanAB血清を含むAIM−Vを用いて培養液を適切な濃度に希釈し、何も固定化していない新しい12.5cm2フラスコ(ベクトン・ディッキンソン社製、353107)に移し、終濃度500U/mLとなるようにIL−2を添加して、継代培養した(培養開始後4日目以降は全ての群にIL−2を添加している)。なお、継代培養操作後の細胞濃度がそれぞれ、培養開始4日目では0.05×106cells/mL、7日目では0.15×106cells/mL、11日目では0.2×106cells/mLになるように希釈を行った。培養開始後15日目には、トリパンブルー染色法にて生細胞数を計測し、培養開始時の細胞数と比較して拡大培養率を算出した。その結果を表1に示す。表1はそれぞれ抗ヒトCD3抗体のみ、抗ヒトCD3抗体とCH−296、抗ヒトCD3抗体と抗ヒトCD28抗体、抗ヒトCD3抗体と抗ヒトCD28抗体とCH−296で刺激した細胞群の増殖率を示したものである。
緩衝液として、ダルベッコPBS粉末(日水製薬社製)よりpH7.4のリン酸緩衝生理食塩水を、0.2Mリン酸二水素ナトリウム水溶液(ナカライテスク社製、317−20より調製)と0.2Mリン酸水素二ナトリウム水溶液(ナカライテスク社製、318−01より調製)を8.15:1.85の比率(容量比)で混合してpH6.2のリン酸ナトリウム緩衝水溶液を、及び0.2M酢酸と0.2M酢酸ナトリウム水溶液を1:4の比率(容量比)で混合してpH5.3の酢酸緩衝水溶液をそれぞれ調製した。これらの緩衝液を用いて終濃度5μg/mLになるように調整した抗ヒトCD28抗体の各溶液を、96穴細胞培養プレート(ベクトン・ディッキンソン社製、353072)の各ウェルに100μLずつ添加後、室温で5時間インキュベートして各pHでの固定化を行った。また同様に、終濃度5μg/mLに調整した抗ヒトCD3抗体の各溶液、もしくは終濃度25μg/mLに調整したCH−296の各溶液を160μLずつ添加後、同じく室温5時間での固定化を行った。これらの固定化が終了後、抗体もしくはCH−296を含む緩衝液を除去し、リン酸緩衝生理食塩水で4倍希釈したブロックエース(大日本製薬社製、UK−B25)を300μLずつ添加して1時間室温に置きブロッキングを行った。その後、溶液を除去し、リン酸緩衝生理食塩水で10倍希釈したブロックエース中に検出用抗体を溶解し、固定化の液量と等量だけ添加した。検出用抗体として、抗ヒトCD3抗体および抗ヒトCD28抗体検出にはHRP−rabbit Anti−Mouse IgG(ZYMED社製、61−6520)を、CH−296の検出にはHRP標識したAnti−Human Fibronectin(Clone FNH3−8、タカラバイオ社製、M115)を使用した。1時間の反応後、再度溶液を除去し、ABTS溶液(SIGMA社製、A1888−2Gより調製)を固定化の液量と等量だけ添加、10分間の反応の後、添加したABTSの半量の150mMのシュウ酸溶液(ナカライテスク社製、25806−74より調製)を添加して反応を停止させた。なお各溶液を除去した際には、リン酸緩衝生理食塩水で3回の洗浄操作を行った。反応停止後、吸光プレートリーダー(MicroReader4、Hyperion社製)で405nmの吸光度を測定した。その結果を表2に示す。表2は抗ヒトCD3抗体、抗ヒトCD28抗体、CH−296について、pH7.4、6.2、5.3の3条件における固定化効率を、吸光度の値で比較したものである。
実施例1と同様の方法でリンパ球を拡大培養した。ただし抗ヒトCD3抗体、抗ヒトCD28抗体およびCH−296の12穴細胞培養プレートへの固定化について、緩衝液としてpH5.3酢酸緩衝水溶液ではなく、pH7.4のリン酸緩衝生理食塩水とpH6.2のリン酸ナトリウム緩衝水溶液を用いた。両緩衝液は実施例2と同様に調製した。また培養開始時に播種する細胞数を1ウェルあたり1×106cellsとした。培養開始後4日目まで、約24時間ごとに培養上清を回収し、ELISA解析に供し、上清中のIL−2濃度を測定した。ELISA解析はELISA Development Kit human IL−2(Genzyme/Techne社製、4904)を使用して行った。その結果を表3に示す。表3は抗ヒトCD3抗体、抗ヒトCD28抗体およびCH−296で細胞を刺激した際のIL−2産生量について、pH7.4のリン酸緩衝生理食塩水とpH6.2のリン酸ナトリウム緩衝水溶液を用いて固定化した場合を比較したものである。
(1)コントロールビーズとCH−296ビーズの調製
Dynabeads M−450 Epoxy(DYNAL社製、140−01)を用いて、CH−296を固定化したビーズ(以下CH−296ビーズと称する)と、抗体やタンパク質を一切固定化せずにブロッキングのみを行ったビーズ(以下コントロールビーズと称する)を調製した。調製は製品付属のプロトコルに従って行った。固定化はCH−296の終濃度が200μg/mLの溶液に4×108beads/mLとなるようにビーズを懸濁し、5℃で18時間インキュベートすることで行った。ブロッキングはヒト血清アルブミン(ブミネート25%、Baxter社製、7783)を用いて行った。
Dynabeads CD3/CD28 T Cell Expander(DYNAL社製、111−31、以下T Cell Expanderと略す)を付属のプロトコルに従って洗浄した後、1%humanAB血清を含むAIM−V(以下1%AIM−Vと略す)に3×106beads/mLとなるように懸濁し、12穴細胞培養プレートに1mL/ウェルずつ加えた。実施例4−(1)で調製したコントロールビーズとCH−296ビーズをT Cell Expanderと同様に洗浄後、1%AIM−Vに1.9×106beads/mLとなるように懸濁した。抗ヒトCD3抗体、抗ヒトCD28抗体共刺激群にはコントロールビーズ懸濁液を、抗ヒトCD3抗体、抗ヒトCD28抗体およびCH−296刺激群にはCH−296ビーズ懸濁液を、12穴細胞培養プレートに1mL/ウェルずつ、T Cell Expander懸濁液に加える形で添加した。実施例1−(1)で調製したPBMCを、1%AIM−Vに1×106cells/mLとなるように懸濁し、ビーズ懸濁液が添加されている12穴細胞培養プレートに1mL/ウェルずつ添加した(合計3mL/ウェル)。その後、終濃度200U/mLとなるように各ウェルにIL−2を添加し、プレートを5%CO2、37℃のインキュベーター内で培養した(培養0日目)。培養開始後4日目、7日目、10日目には以下の方法で継代培養操作を行った。細胞培養液を一部回収し、トリパンブルー染色法にて生細胞数を計測、1%AIM−Vを用いて培養液を適切な濃度に希釈し、12.5cm2フラスコに移し、終濃度200U/mLとなるようにIL−2を添加した。培養液の希釈は、継代操作後の細胞濃度がそれぞれ、4日目では0.05×106cells/mL、7日目では0.1×106cells/mL、10日目では0.15×106cells/mLになるように行った。培養開始後14日目に生細胞数を計測、培養開始時の細胞数と比較して拡大培養率を算出した。その結果を表5に示す。表5はT Cell Expanderとコントロールビーズ、もしくはCH−296ビーズで刺激した細胞群について、14日間の拡大培養後の増殖率を示したものである。
(1)抗ヒトCD3抗体、抗ヒトCD28抗体、CH−296固定化ビーズの調製
実施例4−(1)と同様の方法で行った。ただし固定化は、抗ヒトCD3抗体が25μg/mL、抗ヒトCD28抗体が50μg/mL、CH−296が125μg/mLの終濃度で混在する緩衝液を用いて行った。
実施例4−(2)と同様の方法で行った。ただし培養開始時について、細胞を刺激するビーズには実施例5−(1)で調製したビーズを使用し、培地には0.5%humanAB血清と0.2%のヒト血清アルブミンを含むGT−T503培地(タカラバイオ社製、以下0.5%GT−T503と略す)を用い、細胞数は0.5×106cells/ウェル、培養液量は1.5mL/ウェルとした。ビーズ添加量は0.5×106beads/ウェルと5×106beads/ウェルとなる群を設定した。また継代培養について、継代操作は培養開始後4日目、8日目、11日目に行い、継代後の細胞濃度はそれぞれ、4日目では0.02×106cells/mL、8日目では0.15×106cells/mL、11日目では0.3×106cells/mLとなるように行った。培地には0.5%GT−T503を使用した。培養開始後14日目に生細胞数を計測し、培養開始時の細胞数と比較して拡大培養率を算出した。その結果を表6に示す。表6は、抗ヒトCD3抗体、抗ヒトCD28抗体、CH−296固定化ビーズで刺激した細胞について、0.5×106beadsと5×106beadsで刺激した細胞群の14日間の拡大培養後の増殖率を示したものである。
SEQ ID NO:2 ; Partial region of fibronectin named III-9.
SEQ ID NO:3 ; Partial region of fibronectin named III-10.
SEQ ID NO:4 ; Partial region of fibronectin named III-11.
SEQ ID NO:5 ; Partial region of fibronectin named III-12.
SEQ ID NO:6 ; Partial region of fibronectin named III-13.
SEQ ID NO:7 ; Partial region of fibronectin named III-14.
SEQ ID NO:8 ; Partial region of fibronectin named CS-1.
SEQ ID NO:9 ; Fibronectin fragment named C-274.
SEQ ID NO:10 ; Fibronectin fragment named H-271.
SEQ ID NO:11 ; Fibronectin fragment named H-296.
SEQ ID NO:12 ; Fibronectin fragment named CH-271.
SEQ ID NO:13 ; Fibronectin fragment named CH-296.
SEQ ID NO:14 ; Fibronectin fragment named C-CS1.
SEQ ID NO:15 ; Fibronectin fragment named CHV-89.
SEQ ID NO:16 ; Fibronectin fragment named CHV-90.
SEQ ID NO:17 ; Fibronectin fragment named CHV-92.
SEQ ID NO:18 ; Fibronectin fragment named CHV-179.
SEQ ID NO:19 ; Fibronectin fragment named CHV-181.
SEQ ID NO:20 ; Fibronectin fragment named H-275-Cys.
SEQ ID NO:21 ; Fibronectin fragment named CH-296Na.
Claims (8)
- (a)配列表の配列番号13で表されるアミノ酸配列からなる組換えフィブロネクチンフラグメント、(b)CD3リガンド、及び(c)CD28リガンドの存在下に拡大培養を行なう工程を包含することを特徴とする、リンパ球の製造方法。
- CD3リガンドが抗CD3抗体である請求項1記載の製造方法。
- CD28リガンドが抗CD28抗体である請求項1記載の製造方法。
- リンパ球がリンフォカイン活性化細胞である請求項1記載の製造方法。
- リンパ球に外来遺伝子を導入する工程をさらに包含する請求項1記載の製造方法。
- 外来遺伝子をレトロウィルス、アデノウィルス、アデノ随伴ウィルス、レンチウィルスまたはシミアンウィルスを用いて導入する請求項5記載の製造方法。
- (a)配列表の配列番号13で表されるアミノ酸配列からなる組換えフィブロネクチンフラグメント、(b)CD3リガンド、及び(c)CD28リガンドが固定化された固相。
- 固相が細胞培養プレート、シャーレ、フラスコ、バッグ、ビーズ、メンブレンまたはスライドガラスである請求項7記載の固相。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101525199B1 (ko) * | 2012-09-13 | 2015-06-04 | (주)케이셀바이오 | 100㎖ 이하 말초혈액으로부터 nk세포의 대량 증식 방법 |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100247579A1 (en) * | 2007-05-11 | 2010-09-30 | Hiroshi Shiku | Therapeutic agent for cancer |
US20110027242A1 (en) * | 2008-03-27 | 2011-02-03 | Takara Bio Inc. | Method for production of transfected cell |
WO2010080032A2 (en) * | 2009-01-09 | 2010-07-15 | Stichting Het Nederlands Kanker Instituut | Bead-assisted viral transduction |
EP2236517A1 (en) * | 2009-03-31 | 2010-10-06 | Takara Bio, Inc. | Anti-fibronectin fragment monoclonal antibody |
CN102597223B (zh) * | 2009-09-11 | 2017-05-10 | 宝生物工程株式会社 | 生产天然杀伤细胞的方法 |
JP5805089B2 (ja) * | 2010-08-10 | 2015-11-04 | タカラバイオ株式会社 | 細胞集団の製造方法 |
CN102839153A (zh) * | 2012-09-13 | 2012-12-26 | 济南泰生生物技术有限公司 | 一种以cd3+cd8+为主的活化淋巴细胞的扩增、冻存及复苏方法 |
JP6326811B2 (ja) * | 2013-12-25 | 2018-05-23 | 東洋製罐グループホールディングス株式会社 | 培養容器の製造方法、及び固相化装置 |
EP3091999B1 (en) * | 2014-01-09 | 2021-10-20 | Hadasit Medical Research Services and Development Ltd. | Improved cell compositions and methods for cancer therapy |
WO2015189301A1 (en) * | 2014-06-10 | 2015-12-17 | Polybiocept Ab | Culture medium for cellular immunotherapy |
ES2957890T3 (es) | 2016-04-08 | 2024-01-29 | Univ Emory | Métodos de tratamiento del cáncer y las enfermedades infecciosas mediante terapias celulares |
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WO2018021543A1 (ja) | 2016-07-29 | 2018-02-01 | タカラバイオ株式会社 | 幹細胞の製造に用いられるフィブロネクチンフラグメント |
CN106011061A (zh) * | 2016-08-04 | 2016-10-12 | 广东省第二人民医院 | 一种自然杀伤细胞的体外大规模扩增方法 |
WO2019146673A1 (ja) | 2018-01-25 | 2019-08-01 | タカラバイオ株式会社 | リンパ球の製造方法 |
EP3752252A4 (en) | 2018-02-12 | 2021-11-17 | Hadasit Medical Research Services and Development Ltd. | MODULATION OF SLAMF6 SPLICE VARIANTS FOR CANCER THERAPY |
CN110577592B (zh) * | 2019-10-08 | 2021-11-26 | 广州暨南大学医药生物技术研究开发中心有限公司 | 一种重组人纤连蛋白肽 |
CN113832102B (zh) * | 2021-09-27 | 2024-03-12 | 苏州东岭生物技术有限公司 | Cd3/cd28/dll4磁珠及其制备方法和应用 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0380076A (ja) * | 1989-07-21 | 1991-04-04 | Ortho Pharmaceut Corp | 末梢血液リンパ球細胞増殖刺激法 |
WO2003016511A1 (en) * | 2001-08-15 | 2003-02-27 | Takara Bio Inc. | Method of extended culture for antigen-specific cytotoxic t lumphocytes |
WO2003080817A1 (en) * | 2002-03-25 | 2003-10-02 | Takara Bio Inc. | Process for producing cytotoxic lymphocyte |
JP2004500095A (ja) * | 2000-02-24 | 2004-01-08 | エクサイト セラピーズ, インコーポレイテッド | 細胞の同時の刺激および濃縮 |
WO2005019450A1 (ja) * | 2003-08-22 | 2005-03-03 | Takara Bio Inc. | 細胞傷害性リンパ球の製造方法 |
Family Cites Families (50)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8516421D0 (en) | 1985-06-28 | 1985-07-31 | Biotechnology Interface Ltd | Fibronectins |
DE3788796T2 (de) | 1986-10-20 | 1994-05-05 | Life Technologies Inc | Serumfreies medium zur proliferation von lymphokin-aktivierten töterzellen. |
US5019646A (en) | 1987-08-25 | 1991-05-28 | Regents Of The University Of Minnesota | Polypeptides with fibronectin activity |
JP2561131B2 (ja) | 1988-06-30 | 1996-12-04 | 寳酒造株式会社 | 細胞接着活性ポリペプチド |
US5198423A (en) | 1989-05-26 | 1993-03-30 | Takara Shuzo Co., Ltd. | Functional polypeptide containing a cell binding domain and a heparin binding domain of fibronectin |
US5188959A (en) * | 1989-09-28 | 1993-02-23 | Trustees Of Tufts College | Extracellular matrix protein adherent t cells |
JP3104178B2 (ja) | 1990-03-30 | 2000-10-30 | 寶酒造株式会社 | 機能性ポリペプチド |
JPH04297494A (ja) | 1991-03-26 | 1992-10-21 | Fuji Photo Film Co Ltd | ペプチド誘導体とその用途 |
JP2729712B2 (ja) | 1991-04-23 | 1998-03-18 | 寳酒造株式会社 | 機能性ポリペプチド |
JPH07102131B2 (ja) | 1991-07-15 | 1995-11-08 | 日本石油株式会社 | ヒトリンパ球の癌細胞に対する傷害活性を高める方法 |
JPH06172203A (ja) | 1992-12-02 | 1994-06-21 | Takara Shuzo Co Ltd | フィブロネクチンレセプター産生異常細胞抑制剤 |
JPH06306096A (ja) | 1993-02-26 | 1994-11-01 | Fuji Photo Film Co Ltd | ペプチド誘導体及びその用途 |
GB9315810D0 (en) | 1993-07-30 | 1993-09-15 | Univ London | Stabilised materials |
DE4336399A1 (de) | 1993-10-26 | 1995-04-27 | Augustinus Dr Med Bader | Verfahren zur Verbesserung der Matrixbedingungen bipolar adhärierter Hepatozyten und zur Herstellung eines entsprechend konfigurierten Zellkulturkits |
JP3284700B2 (ja) | 1993-10-28 | 2002-05-20 | トヨタ自動車株式会社 | フロントピラー側部構造 |
US6821778B1 (en) * | 1993-12-01 | 2004-11-23 | The Board Of Trustees Of Leland Stanford Junior University | Methods for using dendritic cells to activate gamma/delta-T cell receptor-positive T cells |
DE4412794A1 (de) * | 1994-04-14 | 1995-12-14 | Univ Ludwigs Albert | Verfahren zur Herstellung von dendritischen Zellen, so erhaltene Zellen und Behälter zur Durchführung dieses Verfahrens |
GB9413029D0 (en) | 1994-06-29 | 1994-08-17 | Common Services Agency | Stem cell immobilisation |
US5827642A (en) * | 1994-08-31 | 1998-10-27 | Fred Hutchinson Cancer Research Center | Rapid expansion method ("REM") for in vitro propagation of T lymphocytes |
US5824547A (en) | 1994-11-29 | 1998-10-20 | Takara Shuzo Co., Ltd. | Method for production of transfected cells |
EP0797450A4 (en) | 1994-12-01 | 2000-02-02 | New England Deaconess Hospital | IN VITRO T-LYMPHOPOIESE SYSTEM |
EP0824594B1 (en) * | 1995-05-04 | 2005-04-06 | The United States of America as Representend by The Secretary of the Navy | Improved methods for transfecting t cells |
US7067318B2 (en) * | 1995-06-07 | 2006-06-27 | The Regents Of The University Of Michigan | Methods for transfecting T cells |
US6692964B1 (en) * | 1995-05-04 | 2004-02-17 | The United States Of America As Represented By The Secretary Of The Navy | Methods for transfecting T cells |
WO1997001194A1 (de) | 1995-06-21 | 1997-01-09 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Elektrochemisches festelektrolyt-zellsystem |
JPH0925299A (ja) | 1995-07-13 | 1997-01-28 | Sumitomo Electric Ind Ltd | Cd44リガンド |
EP0852618A1 (en) | 1995-07-25 | 1998-07-15 | Celltherapy Inc. | Autologous immune cell therapy: cell compositions, methods and applications to treatment of human disease |
DE19537494C2 (de) | 1995-09-25 | 1997-10-02 | Desitin Arzneimittel Gmbh | Kreatin zum Schutz von neuralem Gewebe |
ATE325533T1 (de) | 1995-09-29 | 2006-06-15 | Univ Indiana Res & Tech Corp | Verfahren zum verbesserten virusvermittelten dns- transfer unter verwendung von molekülen mit virus-und zellbindenden domänen |
CN100390290C (zh) * | 1995-11-13 | 2008-05-28 | 宝生物工程株式会社 | 用逆转录病毒将基因转入靶细胞的方法 |
US6734014B1 (en) * | 1996-02-08 | 2004-05-11 | The United States Of America As Represented By The Department Of Health And Human Services | Methods and compositions for transforming dendritic cells and activating T cells |
EP0904350B1 (en) * | 1996-03-04 | 2010-08-04 | Calyx Bio-Ventures Inc. | Modified rapid expansion methods ("modified-rem") for in vitro propagation of t lymphocytes |
AU726198B2 (en) | 1996-03-04 | 2000-11-02 | Targeted Genetics Corporation | Modified rapid expansion methods ("modified-REM") for in vitro propagation of T lymphocytes |
JPH1029952A (ja) | 1996-07-16 | 1998-02-03 | Takara Shuzo Co Ltd | ヒト免疫不全ウイルス感染の制御用組成物および制御方法 |
EP0929664A1 (en) | 1996-09-23 | 1999-07-21 | Ontogeny, Inc. | Hematopoietic stem cells and methods for generating such cells |
US6029472A (en) | 1996-09-27 | 2000-02-29 | Galbreath, Sr.; Charles E. | Refrigerant recycle and reclaim system |
JP2001509677A (ja) | 1997-01-31 | 2001-07-24 | エピミューン,インコーポレイティド | Ctlを活性化するためのペプチドおよびペプチド担持抗原提示細胞 |
TWI239352B (en) | 1997-07-23 | 2005-09-11 | Takara Bio Inc | Gene transfer method with the use of serum-free medium |
AU1865899A (en) | 1997-12-24 | 1999-07-19 | Resolution Pharmaceuticals Inc. | Peptide chelators that predominately form a single stereoisomeric species upon coordination to a metal center |
AU2010699A (en) | 1997-12-24 | 1999-07-19 | Corixa Corporation | Compounds for immunotherapy and diagnosis of breast cancer and methods for theiruse |
CA2340086A1 (en) | 1998-08-11 | 2000-02-24 | The United States Of America, Represented By Department Of Health And Hu Man Services | A method of transducing mammalian cells, and products related thereto |
WO2000056368A1 (fr) | 1999-03-23 | 2000-09-28 | Takara Shuzo Co., Ltd. | Therapeutique genique |
US6797514B2 (en) * | 2000-02-24 | 2004-09-28 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
JP3904374B2 (ja) | 2000-02-29 | 2007-04-11 | 独立行政法人科学技術振興機構 | キラー活性を増強したリンパ球 |
EP1312670A4 (en) | 2000-08-16 | 2005-11-30 | Takara Bio Inc | METHOD FOR THE EXTENSIVE CULTURE OF ANTIGEN-SPECIFIC CYTOTOXIC T CELLS |
WO2002098361A2 (en) * | 2001-06-01 | 2002-12-12 | Xcyte Therapies, Inc. | T cell induced tissue repair and regeneration |
JP4759890B2 (ja) | 2001-09-12 | 2011-08-31 | 大日本印刷株式会社 | パール調印刷物の印刷濃度管理方法 |
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 |
JP4406607B2 (ja) | 2002-08-26 | 2010-02-03 | オンコセラピー・サイエンス株式会社 | ペプチド及びこれを含む医薬 |
JP5271291B2 (ja) | 2010-01-28 | 2013-08-21 | 株式会社エス・エッチ・ティ | 電流検出器 |
-
2006
- 2006-08-10 KR KR1020087006157A patent/KR101279172B1/ko not_active IP Right Cessation
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0380076A (ja) * | 1989-07-21 | 1991-04-04 | Ortho Pharmaceut Corp | 末梢血液リンパ球細胞増殖刺激法 |
JP2004500095A (ja) * | 2000-02-24 | 2004-01-08 | エクサイト セラピーズ, インコーポレイテッド | 細胞の同時の刺激および濃縮 |
WO2003016511A1 (en) * | 2001-08-15 | 2003-02-27 | Takara Bio Inc. | Method of extended culture for antigen-specific cytotoxic t lumphocytes |
WO2003080817A1 (en) * | 2002-03-25 | 2003-10-02 | Takara Bio Inc. | Process for producing cytotoxic lymphocyte |
WO2005019450A1 (ja) * | 2003-08-22 | 2005-03-03 | Takara Bio Inc. | 細胞傷害性リンパ球の製造方法 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101525199B1 (ko) * | 2012-09-13 | 2015-06-04 | (주)케이셀바이오 | 100㎖ 이하 말초혈액으로부터 nk세포의 대량 증식 방법 |
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TW200741000A (en) | 2007-11-01 |
KR20080037086A (ko) | 2008-04-29 |
JPWO2007020880A1 (ja) | 2009-02-26 |
KR101279172B1 (ko) | 2013-06-27 |
CN101243187B (zh) | 2012-07-11 |
US20100150886A1 (en) | 2010-06-17 |
TWI421344B (zh) | 2014-01-01 |
EP1916302A1 (en) | 2008-04-30 |
US8765469B2 (en) | 2014-07-01 |
WO2007020880A1 (ja) | 2007-02-22 |
CN101243187A (zh) | 2008-08-13 |
EP1916302A4 (en) | 2009-10-21 |
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