KR970702060A - DNA 손상제 및 p53을 포함하는 조성물(Compositions comprising DNA damaging agents and p53) - Google Patents

DNA 손상제 및 p53을 포함하는 조성물(Compositions comprising DNA damaging agents and p53)

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KR970702060A
KR970702060A KR1019960705955A KR19960705955A KR970702060A KR 970702060 A KR970702060 A KR 970702060A KR 1019960705955 A KR1019960705955 A KR 1019960705955A KR 19960705955 A KR19960705955 A KR 19960705955A KR 970702060 A KR970702060 A KR 970702060A
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dna damaging
composition
protein
cell
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잭 에이 로쓰
도시요시 후지와라
엘리자베쓰 에이 그림
타파스 무코파디아이
웨이-웨이 쟝
로리 비 오웬-샤우브
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파라비레이
보어드 오브 리전츠, 더 유니버서티 오브 텍사스 시스템
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Abstract

본 발명은 세포, 특히 암세포를 사멸시키기 위한, DNA 손상제 또는 인자와 결합된 종양 억제 유전자의 용도에 대한 것이다. 종양 억제 유전자, p53은 시험관내 및 생체내 모두에서, 화학치료제와 함께 결합되어 재조합 아데노 바이러스-매개된 유전자 전달을 통해 전달된다. 처리된 세포는 특이적 DNA단편화와 함께 아폽토시스를 진행한다. 종양 내로 p53-아데노바이러스 작제물의 직접적인 피하내 주사 이후 DNA 손상제, 시스플라틴의 복강내 투여로 종양의 대량적인 아폽토시스성 파괴를 유도한다. 본 발명은 또한 인체 암의 치료를 위해 복제-결힙성 야생형 p53 아데노바이러스 및 DNA 손상제를 사용하는 유전자 대체법을 결합시키는 섭생의 임상적인 적용법을 제공한다.

Description

DNA 손상제 및 p53을 포함하는 조성물(Compositions comprising DNA damaging agents and p53)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (45)

  1. p53 단백질 또는 유전자 및 DNA 손상제를 세포를 사멸시키기에 효과적인 결합된 양으로 세포와 접촉시킴을 포함하여, 세포를 사멸시키는 방법.
  2. 제1항에 있어서, 상기 세포를 p53 단백질 또는 유전자와, X-선 방사, UV-조사, γ-조사, 마이크로파, 아드리아마이신, 5-플루오로우라실, 에톱포사이드, 캄프토텍신, 악티노마이신-D, 미토마이신 C 또는 시스플라틴과 함께 접촉시키는 방법.
  3. 제2항에 있어서, 상기 세포를 시스플라틴과 함께 p53 단백질 또는 유전자와 접촉시키는 방법.
  4. 제1항에 있어서, 상기 세포를 DNA 손상제와 함께, 세포내에서 p53 단백질을 발현하는 재조합 벡터와 접촉시키는 방법.
  5. 제4항에 있어서, p53-발현 재조합 벡터가 네이키드(naked) DNA 플라스미드, 피로좀 내의 플라스미드, 레트로바이러스 벡터, AAV 벡터 또는 재조합 아데노바이러스 벡터인 방법.
  6. 제5항에 있어서, p53-발현 재조합 벡터가 재조합 아데노바이러스 벡터인 방법.
  7. 제6항에 있어서. p53-발현 재조합 벡터가 사이토메갈로바이러스 IE 프로모터의 조절하에 있는 p53 발현 영역을 포함하는 재조합 아데노바이러스 벡터인 방법.
  8. 제6항에 있어서, 재조합 아데노바이러스 벡터가 p53 발현 영역, 사이토메갈로바이러스 IE 프로모터 및 SV40 초기 폴리아데닐화 시그날을 포함하는 방법.
  9. 제6항에 있어서, 아데노바이러스 복제에 있어 필수적인 유전자 하나 이상이 상기 아데노바이러스 벡터작제물로부터 결실되고 그 자리에 p53 발현 영역이 도입되는 방법.
  10. 제9항에 있어서, 아데노바이러스 벡터의 EIA 및 EIB영역이 결실되고 그 자리에 p53발현 도입되고 있는 방법.
  11. 제6항에 있어서, 재조합 아데노바이러스 벡터가 재조합 아데노바이러스내에 존재하는 방법.
  12. 제1항에 있어서, 세포를 먼저 p53 단백질 또는 유전자와 접촉시킨 다음 연속적으로 DNA 손상제와 접촉시키는 방법.
  13. 제1항에 있어서, 세포를 먼저 DNA 손상제와 접촉시킨 다음 연속적으로 p53 단백질 또는 유전자와 접촉시키는 방법.
  14. 제1항에 있어서, 세포를 p53 단백질 또는 유전자 DNA 손상제와 동시에 접촉시키는 방법
  15. 제1항에 있어서, 세포를 먼저 p53 단백질 또는 유전자를 포함하는 제1조성물과 접촉시키고 DNA 손상제를 포함하는 제2조성물과 접촉시키는 방법.
  16. 제15항에 있어서, 제1또는 제2조성물이 약리학적으로 허용되는 제제중에 분산된 방법.
  17. 제1항에 있어서, 세포를 p53 단백질 또는 유전자를 포함하는 단일 조성물과 DNA 손상제와 함께 접촉시키는 방법.
  18. 제17항에 있어서, 조성물이 약리학적으로 허용되는 제제중에 분산되는 방법.
  19. 제17항에 있어서, 세포를, 세포내에서 p53을 발현하는 제조합 벡터를 포함하는 단일 조성물과 DNA 손상제와 함께 접촉시키는 방법.
  20. 제19항에 있어서, 세포를, 세포내에서 p53을 발현하는 재조합 벡터를 함유하는 재조합 아데노바이러스를 포함하는 단일 조성물과 DNA 손상제와 함께 접촉시키는 방법.
  21. 제1항에 있어서, 세포가 사람 세포인 방법.
  22. 제1항에 있어서, 세포가 악성 세포인 방법.
  23. 제1항에 있어서, 세포가 폐암 세포인 방법.
  24. 제22항에 있어서, 세포가 유방암 세포인 방법.
  25. 제22항에 있어서, 세포가 p53 유전자에서 돌연변이된 방법.
  26. 제21항에 있어서, 세포가 동물내에서 위치하고 p53 단백질 또는 유전자 및 DNA손상제를 약리학적으로 허용되는 형태로 동물에게 투여하는 방법.
  27. 동물에게 p53 단백질 또는 유전자 및 DNA 손상제의 치료학적으로 효과적인 결합물을 투여함을 포함하여, 암을 치료하는 방법.
  28. 제27항에 있어서, 종양 세포내에서 p53을 발현하는 재조합 벡터를 함유하는 재조합 아데노바이러스를 포함하는 약제학적 조성물로 치료학적 유효량으로 종양 부위 내로 주사하고, 종양을 DNA 손상제와 접촉시키는 방법.
  29. 제28항에 있어서, 종양 부위를 X-선 방사, UV-조사, γ-조사 또는 마이크로파로 조사함으로써, 종양을 DNA 손상제와 접촉시키는 방법.
  30. 제28항에 있어서, 동물에게 DNA 손상화합물을 포함하는 치료학적 유효량의 약제학적 조성물을 투여함으로써, 종양을 DNA 손상제와 접촉시키는 방법.
  31. 제28항에 있어서, DNA 손상화합물이 시스플라틴인 방법.
  32. DNA 손상제와 함께 p53 단백질 또는 유전자를 포함하는 조성물.
  33. 제32항에 있어서, 아드리아마이신, 5-플루오로우라실, 에톱포사이드, 캄프토덱신, 악티노마이신-D, 미토마이신 C 또는 시스플라틴과 함께 p53 단백질 또는 유전자를 포함하는 조성물.
  34. 제33항에 있어서, 시스플라틴과 함께 p53 단백질 또는 유전자를 포함하는 조성물.
  35. 제32항에 있어서, DNA 손상제와 함께 동물 세포내에서 p53 단백질을 발현하는 재조합 벡터를 포함하는 조성물.
  36. 제35항에 있어서, 재조합 벡터가 네이키드(naked) DNA 플라스미드, 리포좀 내의 플라스미드, 레트로바이러스 벡터, AAV벡터 또는 재조합 아데노바이러스 벡터인 조성물.
  37. 제36항에 있어서, 재조합 벡터가 재조합 아데노바이러스 벡터인 조성물.
  38. 제37항에 있어서, 재조합 벡터가 재조합 아데노바이러스 입자내에 존재하는 재조합 아데노바이러스 벡터인 조성물.
  39. 제32항에 있어서, 시스플라틴과 함께 재조합 아데노바이러스 입자내에 존재하는 재조합 아데노바이러스 벡터를 포함하는 조성물.
  40. 제32항에 있어서, 약리학적으로 허용되는 제제중에 분산되는 조성물.
  41. 제40항에 있어서, 병변내 투여를 위해 제형화되는 조성물.
  42. 적합한 용기 수단내에, 동물 세포내에서 p53 단백질을 발현하는 재조합 벡터의 약제학적 제제 및 DNA 손상제의 약제학적 제제를 포함하는치료학적 키트.
  43. 제42항에 있어서, 재조합 벡터 및 DNA 손상제가 단일 용기 수단내에 존재하는 키트.
  44. 제42항에 있어서, 재조합 벡터 및 DNA 손상제가 별개의 용기 수단내에 존재하는 키트.
  45. 제42항에 있어서, 동물 세포내에서 p53단백질을 발현하는 재조합 벡터를 포함하는 재조합 아데노바이러스의 약제학적 제제 및 시스플라틴의 약제학적 제제를 포함하는 키트.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019960705955A 1994-04-25 1995-04-24 DNA손상제및p53을포함하는조성물 KR100379174B1 (ko)

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FR2712603B1 (fr) 1993-11-18 1996-02-09 Centre Nat Rech Scient Virus recombinants, préparation et utilisation en thérapie génique.
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CN1147768A (zh) 1997-04-16
US20060182718A1 (en) 2006-08-17
CA2188560C (en) 2011-07-19
BR9507506A (pt) 1997-09-02
CN1209164C (zh) 2005-07-06
JP3847334B2 (ja) 2006-11-22
US6069134A (en) 2000-05-30
NO964527D0 (no) 1996-10-24
DE69535684D1 (de) 2008-02-21
AU2392495A (en) 1995-11-16
SK136796A3 (en) 1997-07-09
EP0760675B2 (en) 2007-12-05
ES2160707T3 (es) 2001-11-16
ES2298174T3 (es) 2008-05-16
EP0760675B1 (en) 2001-08-01
UA43917C2 (uk) 2002-01-15
US6797702B1 (en) 2004-09-28
DE69521994D1 (de) 2001-09-06
JP2003277272A (ja) 2003-10-02
US5747469A (en) 1998-05-05
NO964527L (no) 1996-12-17
CZ295144B6 (cs) 2005-06-15
NO325560B1 (no) 2008-06-16
AU694216B2 (en) 1998-07-16
NZ284709A (en) 1998-08-26
JPH10503476A (ja) 1998-03-31
RU2146149C1 (ru) 2000-03-10
DE69521994T3 (de) 2008-06-26
SK283364B6 (sk) 2003-06-03
EP0760675A1 (en) 1997-03-12
EP1157702B1 (en) 2008-01-09
ATE383167T1 (de) 2008-01-15
DE69535684T2 (de) 2009-01-08
US7109179B2 (en) 2006-09-19
ES2160707T5 (es) 2008-05-16
HUT76258A (en) 1997-07-28
HU9602937D0 (en) 1996-12-30
EP1157702A1 (en) 2001-11-28
KR100379174B1 (ko) 2003-08-02
US20050089511A1 (en) 2005-04-28
ATE203675T1 (de) 2001-08-15
NO20074774L (no) 1996-12-17
PL185749B1 (pl) 2003-07-31
DE69521994T2 (de) 2002-04-04
WO1995028948A1 (en) 1995-11-02
CA2188560A1 (en) 1995-11-02
CZ312196A3 (en) 1997-08-13
PL317105A1 (en) 1997-03-17

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