JPH07509599A - キメラ受容体ポリペプチド,ヒトh13タンパク質,ならびにその使用 - Google Patents
キメラ受容体ポリペプチド,ヒトh13タンパク質,ならびにその使用Info
- Publication number
- JPH07509599A JPH07509599A JP6501727A JP50172794A JPH07509599A JP H07509599 A JPH07509599 A JP H07509599A JP 6501727 A JP6501727 A JP 6501727A JP 50172794 A JP50172794 A JP 50172794A JP H07509599 A JPH07509599 A JP H07509599A
- Authority
- JP
- Japan
- Prior art keywords
- chimeric receptor
- cells
- cell
- polypeptide
- virus
- 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.)
- Granted
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Abstract
Description
Claims (65)
- 1.第一の種に特異的なウイルスに対する受容体のアミノ酸配列を有するポリペ プチドから本質的になり、該受容体の配列が第二の種に特異的なウイルスのウイ ルスenV結合ドメインと結合する少なくとも1つのキメラウイルス受容体結合 部位を含むように修飾されているキメラ受容体ポリペプチドであって、ここで( a)第一の種が第二の種と異なっており、そして(b)該キメラ受容体結合部位 が、該ポリペプチドに第二のウイルスenv結合ドメインに対する結合活性を付 与する、少なくとも第一のアミノ酸残基および第二のアミノ酸残基を含有する、 ことを特徴とするキメラ受容体ポリペプチド。
- 2.前記のウイルスがレトロウイルス、アデノウイルス、またはアデノウイルス 関連ウイルスから選ばれる、請求項1に記載のキメラ受容体ポリペプチド。
- 3.前記のレトロウイルスが白血病ウイルスである、請求項2に記載のキメラ受 容体ポリペプチド。
- 4.前記の白血病ウイルスがマウス白血病ウイルス、ハムスター白血病ウイルス 、およびヒト白血病ウイルスから選ばれる、請求項3に記載のキメラ受容体ポリ ペプチド。
- 5.第一の種がヒト、マウス、ラット、ハムスター、ウサギ、モルモット、ヒヒ 、およびサルよりなる群から選ばれる、請求項1に記載のキメラ受容体ポリペプ チド。
- 6.第一の種がヒトである、請求項5に記載のキメラ受容体ポリペプチド。
- 7.第二の種がヒト以外である、請求項6に記載のキメラ受容体ポリペプチド。
- 8.第二の種がマウス、ラット、ハムスター、ヒヒ、ウサギ、モルモット、およ びサルよりなる群から選ばれる、請求項7に記載のキメラ受容体ポリペプチド。
- 9.第二の種がヒト、マウス、ラット、ハムスター、ヒヒ、ウサギ、モルモット 、およびサルよりなる群から選ばれる、請求項1に記載のキメラ受容体ポリペプ チド。
- 10.少なくとも第一および第二の残基が配列番号:8のアミノ酸210−25 0に対応するアミノ酸を置換する、請求項1に記載のキメラ受容体ポリペプチド 。
- 11.(i)第一の残基がH13(配列番号:8)のPro242に対応する前 記の変異型アミノ酸配列中のアミノ酸を置換するチロシンであり、そして (ii)第二の種に特異的なウイルスの受容体の第二の残基が配列番号:8のV al244、Glu239、Gly240、Gly225よりなる群から選ばれ るアミノ酸を置換する、 請求項10に記載のキメラ受容体ポリペプチド。
- 12.(i)第二の残基がH13(配列番号:8)のGly240に対応するア ミノ酸を置換するバリン、およびH13(配列番号:8)のVal244に対応 するアミノ酸を置換するグルタミンから選ばれる、請求項11に記載のキメラ受 容体ポリペプチド。
- 13.前記の変異型アミノ酸配列がH13(配列番号:8)の膜貫通ドメインに 対応するアミノ酸配列を有する少なくとも1つの膜貫通ドメインペプチドをさら に含む、請求項1に記載のキメラ受容体ポリペプチド。
- 14.キメラ受容体ポリペプチドは、宿主細胞により発現されると、細胞外で前 記のウイルス結合ドメインと結合することができる、請求項1に記載のキメラ受 容体ポリペプチド。
- 15.前記のポリペプチドの配列がH13(配列番号:8)の対応するアミノ酸 配列210−250に対して少なくとも80%の相同性を有する、請求項1に記 載のキメラ受容体ポリペプチド。
- 16.前記のポリペプチドの配列が配列番号:8の対応するアミノ酸配列210 −250に対して少なくとも95%の相同性を有する、請求項15に記載のキメ ラ受容体ポリペプチド。
- 17.真核細胞または組織を、第二の種に特異的なウイルスのウイルス結合ドメ インによる結合を受けやすくする方法であって、(a)該真核細胞または組織を 、invitro、invivoまたはinsituで、請求項1に記載のキメ ラ受容体ポリペプチドをコードする発現可能な変異型核酸により形質転換して、 キメラ受容体細胞または組織をつくり、そして (b)該キメラ受容体ポリペプチドの少なくとも1つのキメラウイルス受容体結 合部位が該キメラ受容体細胞により発現されて、第二の種に特異的なウイルスの 細胞外ウイルス結合ドメインと結合できるような条件を付与する、 ことを含む方法。
- 18.invivo形質転換を、 (i)キメラ受容体細胞または組織への変異型核酸のインジェクション、 (ii)キメラ受容体組織または細胞に対して特異的な組織特異的調節配列の制 御下に変異型核酸を含む組換えレトロウイルスを用いたレトロウイルス感染、 (iii)キメラ受容体組織または細胞への変異型核酸のリボソーム運搬、 (iv)変異型核酸に結合させた、前記の細胞または組織に特異的な抗体をキメ ラ受容体組織または細胞に接触させること、または (v)変異型核酸に結合させた、前記の細胞または組織に特異的な抗体を前記の 組織または細胞に接触させること、から選ばれた方法により行う、請求項17に 記載の方法。
- 19.insituまたはinvitro形質転換を、(i)キメラ受容体細胞 または組織への変異型核酸のインジェクション、 (ii)キメラ受容体組織または細胞に対して特異的な組織特異的調節配列の制 御下に変異型核酸を含む組換えレトロウイルスを用いたレトロウイルス感染、 (iii)変異型核酸のリボソーム運搬、(iv)前記の核酸を含む前記の組織 または細胞のトランスフェクション、または (v)変異型核酸に結合させた、前記の細胞または組織に特異的な抗体を前記の 組織または細胞に接触させること、から選ばれた方法により行う、請求項17に 記載の方法。
- 20.真核細胞または組織が哺乳類、昆虫、鳥類および酵母よりなる群から選ば れる、請求項17に記載の方法によりつくられたキメラ受容体細胞または組織。
- 21.哺乳類の細胞または組織がヒト、霊長類、ハムスター、ウサギ、■歯類、 ウシ、ブタ、ヒツジ、ウマ、ヤギ、イヌ、またはネコ由来のものである、請求項 20に記載のキメラ受容体細胞。
- 22.キメラ受容体細胞または組織に少なくとも1種の治療薬または診断薬を伝 達する方法であって、 (a)請求項20に記載のキメラ受容体細胞または組織を用意し、(b)該キメ ラ受容体細胞または組織を、invitro、invivoまたはinsitu で、非ヒトウイルスのenV結合ドメインおよび少なくとも1種の治療薬または 診断薬を含む運搬ベクターと接触させ、これにより該運搬ベクターが該キメラ修 飾細胞または組織と結合し、かつ治療薬または診断薬が該キメラ受容体細胞また は組織に対して治療または診断効果を及ぼすようにする、ことからなる方法。
- 23.治療薬が治療用核酸であり、そしてキメラ受容体細胞に対する治療効果が (i)DNA配列の転写を阻止すること、(ii)RNA配列の翻訳を阻止する こと、(iii)RNAまたはDNA配列の逆転写を阻止すること、(iv)タ ンパク質の翻訳後修飾を阻止すること、(v)DNA配列の転写を誘導すること 、(vi)RNA配列の翻訳を誘導すること、(vii)RNAまたはDNA配 列の逆転写を誘導すること、(viii)タンパク質の翻訳後修飾を誘導するこ と、(ix)該核酸をRNAとして転写すること、(x)該核酸をタンパク質と して翻訳すること、および(xi)キメラ受容体細胞の染色体へ該核酸を組み込 むこと、よりなる群から選ばれる、請求項22に記載の方法。
- 24.運搬ベクターが組換え型の非ヒト特異的ウイルスであり、その結果、キメ ラ受容体細胞または組織への非ヒト特異的ウイルスの結合が該修飾受容体細胞の 感染を引き起こし、かつ該キメラ受容体細胞において治療用核酸の治療効果を生 じさせる、請求項23に記載の方法。
- 25.運搬ベクターが(i)env結合ドメインと、該ドメインにリンカーによ って結合された(ii)治療薬または診断薬を含み、その結果、前記の接触が治 療または診断効果をもたらすものである、請求項22に記載の方法。
- 26.運搬ベクターがさらにリボソームからなり、該リボソームがenv結合ド メインと治療薬または診断薬を含み、その結果、env結合ドメインがキメラ受 容体細胞のキメラ受容体結合部位に結合することができる、請求項22に記載の 方法。
- 27.前記の接触が治療上有効な量の治療用核酸の発現産物を発現する前記の修 飾受容体細胞または組織をもたらす、請求項23に記載の方法。
- 28.治療用核酸が異常な形のタンパク質に関連した疾病を治すように作用する 正常な形のタンパク質をコードしている、請求項23に記載の方法。
- 29.治療用核酸がキメラ受容体細胞または組織を選択的に死滅させるように作 用する毒素をコードしている、請求項23に記載の方法。
- 30.前記のキメラ細胞が病的な細胞である、請求項29に記載の方法。
- 31.治療用核酸が上皮増殖因子、インターロイキン−2、インターロイキン− 4、インターロイキン−6、組織増殖因子−α、インスリン増殖因子−1または 繊維芽細胞増殖因子から選ばれた増殖因子をコードしている、請求項30に記載 の方法。
- 32.前記の毒素がリシン、シュードモナス外毒素、ジフテリア毒素およびチミ ジンキナーゼの少なくとも1種から選ばれる毒素の少なくとも1つの機能的な細 胞毒性ドメインを含む組換え型の毒素または毒素フラグメントである、請求項3 0に記載の方法。
- 33.治療用核酸がキメラ受容体細胞または組織における異常なタンパク質の発 現を阻止するように作用するアンチセンスヌクレオチドをコードしている、請求 項23に記載の方法。
- 34.治療用核酸がキメラ受容体細胞または組織における異常なタンパク質の発 現を阻止するように作用する一本鎖のリボソーム阻害タンパク質をコードしてい る、請求項23に記載の方法。
- 35.治療用核酸がサイトカインをコードしている、請求項23に記載の方法。
- 36.治療用核酸が増殖因子をコードしている、請求項23に記載の方法。
- 37.前記のウイルスが組換え白血病レトロウイルスである、請求項22に記載 の方法。
- 38.前記の治療薬が病的な細胞または組織としてのキメラ受容体細胞または組 織を死滅させるように作用する毒素である、請求項22に記載の方法。
- 39.病的な細胞が腫瘍細胞である、請求項38に記載の方法。
- 40.前記の毒素がリシン、シュードモナス外毒素およびジフテリア毒素の少な くとも1種から選ばれる毒素の少なくとも1つの機能的な細胞毒性ドメインを含 む組換え型の毒素または毒素フラグメントである、請求項38に記載の方法。
- 41.前記の診断薬がinvivo、insituまたはinvitroで検出 可能な標識である、請求項22に記載の方法。
- 42.検出可能な標識が放射性標識、酵素標識または蛍光標識である、請求項4 1に記載の方法。
- 43.請求項1に記載のキメラ受容体ポリペプチドをコードするヌクレオチド配 列を含む組換え核酸。
- 44.請求項43の核酸を含有する宿主細胞。
- 45.宿主細胞が哺乳類、酵母、鳥類または昆虫の細胞から選ばれるものである 、請求項44に記載の宿主細胞。
- 46.前記の核酸が宿主細胞において前記の受容体ポリペプチドとして発現され 、前記のenv結合ドメインを含む受容体結合分子が該受容体ポリペプチドと結 合する、請求項44に記載の宿主細胞。
- 47.哺乳類の細胞がヒト、霊長類または齧歯類の細胞から選ばれるものである 、請求項45に記載の宿主細胞。
- 48.請求項1に記載のキメラ受容体ポリペプチドに特異的なエピトープと結合 するキメラ受容体抗体、その抗イディオタイプ抗体またはフラグメント。
- 49.モノクローナルである、請求項48に記載のキメラ受容体抗体、その抗イ ディオタイプ抗体またはフラグメント。
- 50.invivo、insituまたはinvitroで検出可能な標識によ り標識されている、請求項48に記載のキメラ受容体抗体、その抗イディオタイ プ抗体またはフラグメント。
- 51.検出可能な標識が放射性標識、酵素標識または蛍光標識である、請求項5 0に記載の抗体。
- 52.請求項1に記載のキメラ受容体ポリペプチドの生産方法であって、 (a)請求項1のキメラ受容体ポリペプチドをコードする核酸を発現可能な形態 で含む組換え宿主を培養し、(b)該組換え宿主を培養することにより、該キメ ラ受容体ポリペプチドを回収可能な量で発現させ、そして(c)該宿主または培 養物から該キメラ受容体ポリペプチドを回収する、 ことからなる方法。
- 53.(d)前記のキメラ受容体ポリペプチドを精製する、ことをさらに含む、 請求項52に記載の方法。
- 54.試料中に含まれる請求項1のキメラ受容体ポリペプチドのエピトープに特 異的な抗体の検出方法であって、(a)該試料を、固体の担体に付着させた請求 項1のキメラ受容体ポリペプチドまたはそのフラグメントと接触させ、これによ り該抗体を該ポリペプチドと結合させ、そして(b)該担体に付着させた該キメ ラ受容体ポリペプチドと結合している試料中の該抗体を検出する、 ことからなる方法。
- 55.試料中に含まれる請求項1のキメラ受容体ポリペプチドのエピトープに特 異的な抗体の回収方法であって、(a)該試料を、固体の担体に付着させた請求 項1のキメラ受容体ポリペプチドまたはそのフラグメントと接触させ、これによ り該抗体を該キメラ受容体ポリペプチドと結合させ、そして(b)該担体に付着 させた該キメラ受容体ポリペプチドと結合している試料中の該抗体を回収する、 ことからなる方法。
- 56.生殖細胞と体細胞の実質的にすべてが請求項1のキメラ受容体ポリペプチ ドをコードするヌクレオチド配列を含有する組換え核酸を含んでいるトランスジ ェニック非ヒト哺乳動物。
- 57.前記の組換え核酸が胚形成期に前記の哺乳動物または該哺乳動物の祖先に 導入されたものである、請求項56に記載のトランスジェニック哺乳動物。
- 58.配列番号:8のH13ポリペプチドのアミノ酸配列に実質的に相当するア ミノ酸配列を有するポリペプチドからなる、単離したまたは組換え型のH13ポ リペプチド。
- 59.少なくとも1種の請求項1のキメラ受容体ポリペプチド、ならびに製剤上 許容される担体を含有してなる、レトロウイルス感染を予防または治療するのに 有用な医薬組成物。
- 60.レトロウイルス阻止量の請求項59に記載の医薬組成物を投与することか らなる、被験者におけるレトロウイルス感染の予防または治療方法。
- 61.レトロウイルスを、細胞をレトロウイルス感染から防御するのに十分な量 の請求項1のキメラ受容体ポリペプチドと接触させることからなる、レトロウイ ルスの感染性を抑制する方法。
- 62.レトロウイルスがヒト免疫不全ウイルスである、請求項61に記載の方法 。
- 63.前記の接触をinvivo、invitroまたはinsituで行う、 請求項61に記載の方法。
- 64.検出可能に標識されたキメラ受容体ポリペプチドと結合し得る、試料中に 含まれるヒトレトロウイルス、レトロウイルスタンパク質またはそれから誘導さ れるペプチドの検出方法であって、(a)試料を、検出可能に標識された請求項 1のキメラ受容体ポリペプチドと接触させ、これにより該標識されたキメラ受容 体ポリペプチドを該レトロウイルス、レトロウイルスタンパク質またはレトロウ イルスペプチドと結合させて、検出可能に標識されたレトロウイルス、レトロウ イルスタンパク質またはレトロウイルスペプチドを形成させ、そして (b)該標識されたキメラ受容体ポリペプチドに結合している、該試料中の標識 されたレトロウイルス、レトロウイルスタンパク質またはレトロウイルスペプチ ドを検出する、ことからなる方法。
- 65.検出可能に標識されたH13ポリペプチドと結合し得る、試料中に含まれ るヒトレトロウイルス、レトロウイルスタンパク質またはそれから誘導されるペ プチドの検出方法であって、(a)試料を、検出可能に標識された請求項58の キメラ受容体ポリペプチドと接触させ、これにより該標識された受容体ポリペプ チドを該レトロウイルス、レトロウイルスタンパク質またはレトロウイルスペプ チドと結合させて、検出可能に標識されたレトロウイルス、レトロウイルスタン パク質またはレトロウイルスペプチドを形成させ、そして (b)該標識されたヒト受容体ポリペプチドに結合している、該試料中に含まれ る標識されたレトロウイルス、レトロウイルスタンパク質またはレトロウイルス ペプチドを検出する、ことからなる方法。
Applications Claiming Priority (3)
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US89907592A | 1992-06-11 | 1992-06-11 | |
US899,075 | 1992-06-11 | ||
PCT/US1993/005569 WO1993025682A2 (en) | 1992-06-11 | 1993-06-11 | Chimeric receptor polypeptides, human h13 proteins and uses thereof |
Publications (2)
Publication Number | Publication Date |
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JPH07509599A true JPH07509599A (ja) | 1995-10-26 |
JP3623230B2 JP3623230B2 (ja) | 2005-02-23 |
Family
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JP50172794A Expired - Fee Related JP3623230B2 (ja) | 1992-06-11 | 1993-06-11 | キメラ受容体ポリペプチド,ヒトh13タンパク質,ならびにその使用 |
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EP (1) | EP0644936A1 (ja) |
JP (1) | JP3623230B2 (ja) |
AU (1) | AU4532293A (ja) |
CA (1) | CA2137547A1 (ja) |
SG (1) | SG52708A1 (ja) |
WO (1) | WO1993025682A2 (ja) |
Cited By (1)
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JP2011501958A (ja) * | 2007-10-29 | 2011-01-20 | バージニア テック インテレクチュアル プロパティーズ インコーポレーテッド | ブタDC−SIGN、ICAM−3およびLSECtinならびにそれらの使用 |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
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US5753499A (en) * | 1994-12-23 | 1998-05-19 | New York University | Viral vector complexes having adapters of predefined valence |
US6096548A (en) * | 1996-03-25 | 2000-08-01 | Maxygen, Inc. | Method for directing evolution of a virus |
AU7127798A (en) * | 1997-04-18 | 1998-11-13 | President And Fellows Of Harvard College | Bifunctional polypeptides for cell-specific viral targeting |
US6060316A (en) * | 1998-06-09 | 2000-05-09 | President And Fellows Of Harvard College | Methods of targeting of viral entry |
KR102596125B1 (ko) * | 2012-09-04 | 2023-10-30 | 더 스크립스 리서치 인스티튜트 | 표적화된 바인딩 특이도를 갖는 키메라 폴리펩타이드들 |
KR101859223B1 (ko) * | 2016-11-29 | 2018-06-01 | 단디바이오사이언스 주식회사 | 고병원성 인플루엔자 바이러스 검출용 마커 및 이의 용도 |
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CA2097705A1 (en) * | 1990-12-14 | 1992-06-15 | Daniel Meruelo | Human retrovirus receptor and dna coding therefor |
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1993
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- 1993-06-11 SG SG1996008128A patent/SG52708A1/en unknown
- 1993-06-11 WO PCT/US1993/005569 patent/WO1993025682A2/en not_active Application Discontinuation
- 1993-06-11 EP EP93915287A patent/EP0644936A1/en not_active Withdrawn
- 1993-06-11 AU AU45322/93A patent/AU4532293A/en not_active Abandoned
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JP2011501958A (ja) * | 2007-10-29 | 2011-01-20 | バージニア テック インテレクチュアル プロパティーズ インコーポレーテッド | ブタDC−SIGN、ICAM−3およびLSECtinならびにそれらの使用 |
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Publication number | Publication date |
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EP0644936A1 (en) | 1995-03-29 |
CA2137547A1 (en) | 1993-12-23 |
SG52708A1 (en) | 1998-09-28 |
AU4532293A (en) | 1994-01-04 |
JP3623230B2 (ja) | 2005-02-23 |
WO1993025682A2 (en) | 1993-12-23 |
WO1993025682A3 (en) | 1994-03-17 |
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