JPH09500618A - 異種移植に対する寛容性の発現のための代理寛容形成 - Google Patents
異種移植に対する寛容性の発現のための代理寛容形成Info
- Publication number
- JPH09500618A JPH09500618A JP7500907A JP50090795A JPH09500618A JP H09500618 A JPH09500618 A JP H09500618A JP 7500907 A JP7500907 A JP 7500907A JP 50090795 A JP50090795 A JP 50090795A JP H09500618 A JPH09500618 A JP H09500618A
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.供与動物から受容動物に器官を異種移植する方法であって、前記受容体は供 与体組織に対して免疫寛容とされており、 a) 受容体から第1の細胞集団を集め、前記第1の細胞集団はリンパ球始原細 胞を含むが代理動物からの組織に対して特異的に細胞毒性を有する細胞が減少し ており; b) 前記第1の細胞集団を前記代理体に投与し、前記代理体は免疫欠失状態に あり; c) 前記代理体において免疫反応性状態(immune competence)を発達させ; d) 前記免疫反応性代理体から第2の細胞集団を集め、前記第2の細胞集団は 免疫抑制成分を含み、前記免疫抑制成分は前記代理体の組織に対する前記受容体 の免疫応答を特異的に抑制し; e) 前記第2の細胞集団を前記受容体に注入し; f) 前記代理体と免疫原的に同一の供与動物から器官を切除し;そして g) 前記器官を前記異種移植受容体に移植する; の各工程を含む方法。 2.供与動物から、前記供与動物とは同系ではない受容動物に器官を移植する方 法であって、 a) 前記受容動物に、代理動物から得た、前記供与動物に対する前記受容動物 の免疫応答を特異的に抑制する免疫抑制成分を含む細胞集団を投与し、前記代理 動物は前記受容動物に由来するリンパ球を含むキメラ動物であり;そして b) 器官を前記供与動物から前記受容動物に移植し、このことにより前記器官 に対する前記受容動物の免疫応答が減少する; の各工程を含む方法。 3.細胞集団が、サプレッサーT細胞、ヴィトー細胞、抗イディオタイプ抗体を 産生する細胞、および抗イディオタイプ抗体からなる群より選択される免疫抑制 成分を含む、請求項2記載の方法。 4.前記代理動物が前記供与動物と同一の動物である、請求項2記載の方法。 5.前記代理動物および前記受容動物が異なる種からのものである、請求項2記 載の方法。 6.前記代理動物が前記供与動物と同一の動物である、請求項5記載の方法。 7.前記代理動物および前記供与動物が異なる動物個体である、請求項5記載の 方法。 8.前記供与動物および前記受容動物が同一の種からのものである、請求項5記 載の方法。 9.前記代理動物が、前記供与動物の両方の遺伝的親に由来するリンパ球をも含 む、請求項2記載の方法。 10.前記器官が細胞懸濁物であり、前記代理動物が前記遺伝的親の1より多い 子孫に由来する細胞を含む、請求項9記載の方法。 11.前記代理動物が生まれたときに前記供与動物が成熟している、請求項9記 載の方法。 12.前記供与動物および前記代理動物が異なる個体であり、前記器官が細胞集 団であり、そして前記細胞集団が、前記受容動物に移植する前に前記代理動物中 で培養することにより拡大される、請求項2記載の方法。 13.前記器官が、膵島細胞および肝細胞からなる群より選択される、請求項1 2記載の方法。 14.前記器官が骨髄である、請求項12記載の方法。 15.供与動物から、前記供与動物とは同系ではない受容動物に器官を移植する 方法であって、 a) 前記受容動物に、代理動物から得た、前記供与動物に対する前記受容動物 の免疫応答を特異的に抑制する免疫抑制成分を含む細胞集団を投与し、前記代理 動物は、受容動物と同一の種の動物の組に由来するリンパ球を含むキメラ動物で あり、前記動物の組は複数の組織型を有し;そして b) 器官を前記供与動物から前記受容動物に移植し、このことにより前記器官 に対する前記受容動物の免疫応答が減少する; の各工程を含む方法。 16.受容動物による、供与動物から移植された器官の免疫拒絶を抑制するため のキットであって、代理動物から得た細胞集団を含む免疫抑制組成物を含み、前 記代理動物は前記受容動物に由来するリンパ球を含むキメラ動物であり、前記細 胞集団は前記供与動物に対する前記受容動物の免疫応答を特異的に抑制する免疫 抑制成分を含み、前記免疫抑制組成物は前記受容動物に注入するのに適当なもの であることを特徴とするキット。 17.前記免疫抑制組成物が、前記代理体の免疫反応性細胞を実質的に含まない 、請求項16記載のキット。 18.受容動物による、前記受容動物と同系ではない供与動物から移植された器 官の免疫拒絶を抑制するための請求項16記載の免疫抑制組成物を製造する方法 であって、 a) 前記受容動物から第1の細胞集団を集め、前記第1の細胞集団はリンパ球 始原細胞を含み; b) 前記第1の細胞集団を代理動物に投与し、前記代理体は免疫欠失状態にあ り; c) 前記代理体において免疫反応性状態を発達させ; d) 前記免疫反応性代理体から第2の細胞集団を集め、前記第2の細胞集団は 前記供与体の組織に対する前記受容体の免疫応答を特異的に抑制する免疫抑制成 分を含み;そして e) 前記第2の細胞集団からの免疫抑制成分を、前記受容動物に注入するのに 適当な組成物中に入れる; の各工程を含む方法。 19.前記受容動物に注入するのに適当な組成物が感染性因子を含まない、請求 項18記載の方法。 20.免疫抑制成分が、サプレッサーT細胞、ヴィトー細胞、抗イディオタイプ 抗体を産生する細胞、および抗イディオタイプ抗体からなる群より選択される、 請求項18記載の方法。 21.前記第1の細胞集団を前記代理体に投与する前に、前記代理動物からの組 織に特異的に細胞毒性を有する細胞の少なくとも一部が前記第1の細胞集団から 除去されている、請求項18記載の方法。 22.前記第2の細胞集団を集める工程の前に、前記受容体から新たなリンパ球 を集め、前記新たなリンパ球を前記発達させた代理体に注入する工程をさらに含 む、請求項18記載の方法。 23.前記免疫欠失代理体が胎児動物である、請求項18記載の方法。 24.免疫欠失代理体が、新生児動物、幼若動物および成体動物からなる群より 選択され、前記動物は致死量の放射線または化学療法を受けた後に細胞集団の骨 髄移植を受けており、前記細胞集団は前記異種移植受容体、前記異種移植供与体 、および前記代理体から選択される生物からの増血性リンパ球様細胞を含み、ま たは前記細胞集団は2以上のこれらの生物からの増血性リンパ球様細胞の混合物 を含む、請求項18記載の方法。 25.前記代理体が前記供与動物と同一の動物である、請求項18記載の方法。 26.前記第1の細胞集団が、追加的に複数の免疫不全代理体に投与され、前記 複数の代理体を免疫反応性生物に発達させる、請求項18記載の方法。 27.前記第2の細胞集団を集める工程の前に、さらに i) 免疫応答性に発達した複数の代理体からそれぞれ血液または脾臓標本を集 め; ii) それぞれの血液標本を試験して、前記受容動物の細胞の移植(engr aftment)の程度を決定し、かつそれぞれの血液標本におけるリンパ球の 成熟の程度を決定し; iii) 複数の発達した代理体のそれぞれの細胞を、受容動物細胞と供与動物 細胞との間の免疫反応性の特異的抑制について試験し; vi) それぞれの血液標本を試験する工程に応じて、複数の発達した代理体の 選択された組を選択し、前記選択された組は比較的高い程度の移植および比較的 高い免疫抑制を有し; v) 前記異種移植受容体から新たなリンパ球を集め、前記新たなリンパ球を発 達した代理体の選択された組に注入することにより、それぞれの発達した代理体 に対する選択された組の移植片対宿主疾患(GvHD)について試験し;そして vi) 異種移植受容体からのリンパ球の注入に対する応答における最も低い程 度のGvHDに基づいて、発達した代理体の選択された組から最も良い発達した 代理体を同定する; の各工程を含む方法。 28.前記供与動物の両方の遺伝的親に由来するリンパ球が、免疫欠失状態にあ る前記代理動物に、前記第1の細胞集団と実質的に同時に投与される、請求項1 8記載の方法。 29.前記器官が細胞懸濁物であり、細胞懸濁物が前記遺伝的親の1より多い子 孫からの細胞を含む、請求項28記載の方法。 30.前記代理動物が生まれたときに前記供与動物が成熟している、請求項28 記載の方法。 31.前記供与動物および前記代理動物が異なる個体であり、前記器官が細胞懸 濁物であり、そして前記細胞懸濁物が、前記受容動物に拡大された細胞懸濁物を 移植する前に前記代理動物中で培養することにより拡大される、請求項18記載 の方法。 32.前記器官が膵島細胞および肝細胞からなる群より選択される、請求項31 記載の方法。 33.前記器官が骨髄である、請求項31記載の方法。 34.受容動物による、前記受容動物と同系ではない供与動物から移植された器 官の免疫拒絶を抑制するための免疫抑制組成物を製造する方法であって、 a) 代理動物に、前記受容動物と同一の種の動物の組に由来するリンパ球を投 与し、前記動物の組は複数の組織型を有し、前記代理体は免疫欠失状態にあり; b) 前記代理体において免疫反応性状態を発達させ; c) 前記免疫反応性代理体から第2の細胞集団を集め、前記第2の細胞集団は 、前記供与体の組織に対する前記受容体の免疫応答を特異的に抑制する免疫抑制 成分を含み;そして d) 前記第2の細胞集団からの免疫抑制成分を、前記受容動物に注入するため に適当な組成物中に入れる; の各工程を含む方法。 35.受容動物に器官を移植するためのキットであって、前記受容体とは異なる 種から切除した身体器官、および前記切除された器官を前記受容動物に移植する のに適当な状態に保存するのに十分な量の灌流溶液を含み、前記器官の複数のレ ジデント細胞は前記受容体と同一の種からの細胞であり、前記レジデント細胞は 内皮細胞、単球、樹状細胞、およびリンパ球様細胞から選択され、前記身体器官 は前記受容動物に移植するのに適当なものであることを特徴とするキット。 36.前記複数のレジデント細胞が前記受容動物と同系である、請求項35記載 のキット。 37.切除器官とは同系ではない受容動物に移植するための請求項35記載の切 除器官を製造する方法であって、 a) 前記受容動物から細胞集団を集め、前記第1の細胞集団はリンパ球始原細 胞を含み; b) 前記細胞集団を代理動物に投与し、前記代理体は免疫欠失状態にあり; c) 前記代理体において免疫反応性状態を発達させ; d) 前記免疫反応性代理体から器官を切除し、前記器官は前記受容動物に由来 する少なくとも複数の細胞とともに集団化(polulated)されており; そして e) 前記切除器官が前記受容動物に移植するのに適当な条件において保存され るように前記器官を灌流溶液に入れる; の各工程を含む方法。 38.前記代理体に前記細胞集団を投与する前に、前記代理動物からの組織に特 異的に細胞毒性を有する細胞の少なくとも一部が前記細胞集団から除去されてい る、請求項37記載の方法。 39.切除器官とは同系ではない受容動物に移植するための切除器官を製造する 方法であって、 a) 前記受容動物と同一の種の動物から細胞集団を集め、前記細胞集団はリン パ球始原細胞を含み; b) 前記細胞集団を代理動物に投与し、前記代理体は免疫欠失状態にあり; c) 前記代理体において免疫反応性状態を発達させ; d) 前記免疫反応性代理体から器官を切除し、前記器官は前記受容動物に由来 する少なくとも複数の細胞とともに集団化されており;そして e) 前記切除された器官が前記受容動物に移植するのに適当な条件において保 存されるように前記器官を灌流溶液に入れる; の各工程を含む方法。 40.前記代理体に前記細胞集団を投与する前に、前記代理動物からの組織に特 異的に細胞毒性を有する細胞の少なくとも一部が前記細胞集団から除去されてい る、請求項39記載の方法。 41.受容体と同一の種の動物の組に由来するリンパ球が、免疫欠失状態にある 前記代理動物に前記細胞集団と実質的に同時に投与され、前記動物の組が複数の 組織型を有する、請求項39記載の方法。 42.前記受容動物が重症の熱傷を有するヒトであり、前記代理動物が非ヒト哺 乳動物であり、かつ前記器官が前記受容体の熱傷領域に適用するための前記非ヒ ト哺乳動物からの皮膚の移植片であり、前記皮膚の少なくとも複数のレジデント 細胞が前記患者と同一の種に由来する細胞である、請求項41記載の方法。 43.前記供与動物および前記代理動物が異なる個体であり、前記器官が細胞集 団であり、前記細胞集団が、前記受容動物に移植する前に前記代理動物中で培養 することにより拡大されている、請求項39記載の方法。 44.前記器官が膵島細胞および肝細胞からなる群より選択される、請求項43 記載の方法。 45.劇症肝炎を有する患者の補充治療法であって、肝壊死が継続する間周期的 に、前記患者に請求項44記載の方法により製造された肝細胞を移植することを 含む方法。 46.前記器官が骨髄である、請求項43記載の方法。
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AU781909B2 (en) * | 2000-01-25 | 2005-06-23 | Board Of Regents Of The University Of Nebraska, The | Pre-transplant accommodated organs resistant to anti-donor immunity |
WO2001065934A2 (en) * | 2000-03-09 | 2001-09-13 | Lee Walters | Applications of immune system tolerance to treatment of various diseases |
IL142802A (en) * | 2000-04-27 | 2015-01-29 | Enzo Therapeutics Inc | Use of one or more HBV antigens for the preparation of oral pharmaceutical preparations for the treatment of a person with active HBV infection or hepatocellular carcinoma |
EP1303183A1 (de) * | 2000-07-27 | 2003-04-23 | Apogene GmbH & Co. KG | Somatischer klonierungs-gentransfer zur produktion von rekombinanten proteinen, zellen und organen |
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US20040136972A1 (en) * | 2001-09-07 | 2004-07-15 | Yeda Research And Development Co. Ltd. | Methods of treating disease by transplantation of developing allogeneic or xenogeneic organs or tissues |
US20040161419A1 (en) * | 2002-04-19 | 2004-08-19 | Strom Stephen C. | Placental stem cells and uses thereof |
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US20060148080A1 (en) * | 2004-12-30 | 2006-07-06 | Paul Diamond | Methods for supporting and producing human cells and tissues in non-human mammal hosts |
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US4624917A (en) * | 1982-02-17 | 1986-11-25 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Process for the production of human T-cell growth factor |
JPS6339820A (ja) * | 1986-08-05 | 1988-02-20 | Kingo Yoshida | 拒絶反応抑制,幼若細胞移植による不老長寿法 |
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EP0700297B1 (en) | 2002-07-31 |
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