KR880000582A - Methods and ligands to promote proliferation of B-cells - Google Patents

Methods and ligands to promote proliferation of B-cells Download PDF

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KR880000582A
KR880000582A KR870005969A KR870005969A KR880000582A KR 880000582 A KR880000582 A KR 880000582A KR 870005969 A KR870005969 A KR 870005969A KR 870005969 A KR870005969 A KR 870005969A KR 880000582 A KR880000582 A KR 880000582A
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에이. 레드베터 제프리
에이. 클라크 에드워드
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브래들리 더블유. 시몬스
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Abstract

내용 없음No content

Description

B-세포의 증식을 촉진시키는 방법 및 배위자Methods and ligands to promote proliferation of B-cells

본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음As this is a public information case, the full text was not included.

제1도는 청색형광의 기록과 적색형광의 기록에 대한 세포의 수를 도시한 것임.Figure 1 shows the number of cells for the recording of blue fluorescence and the recording of red fluorescence.

제3도는 Bp50 발현의 2가지 색상의 면역형광 분석도.3 is an immunofluorescence assay of two colors of Bp50 expression.

제5도는 B-세포활성 신호후에 부가된 증식 촉진효과를 나타낸 곡선.5 is a curve showing the proliferation promoting effect added after the B-cell activity signal.

Claims (67)

(a) 모노클로날 항세 G28-5로 정의되는 Bp50, 즉 50킬로달톤 B-세포표면 항원에 결합되고, (b)활성화된 B-세포에 결합시킴으로써 세포사이클이 역전되도록 활성화된 B-세포를 자극시켜 B-세포의 증식을 촉진시키는 순수한 배위자.(a) binds Bp50, defined as monoclonal antibody G28-5, that is, 50 kilodalton B-cell surface antigen, and (b) activates B-cells that are activated to reverse the cell cycle by binding to activated B-cells. Pure ligand that stimulates the proliferation of B-cells. 제1항에 있어서, 항체분자 또는 항체분자의 FV,Fab,F(ab')2또는 Fab' 부분으로 구성된 것이 특징인 배위자.The ligand of claim 1, wherein the ligand is composed of an antibody molecule or an FV, Fab, F (ab ') 2 or Fab' portion of the antibody molecule. 제2항에 있어서, 항체분자가 모노클로날 항체분자 또는 모노클로날 항체분자의 Fv,Fab,F(ab')2또는 Fab' 부분으로 구성된 것이 특징인 배위자.3. The ligand of claim 2, wherein the antibody molecule comprises a monoclonal antibody molecule or a Fv, Fab, F (ab ') 2 or Fab' portion of a monoclonal antibody molecule. G28-5, 또는 이것의 Fv,Fab,F(ab')2또는 Fab' 부분으로 구성된 것이 특징인 제3항의 모노클로날 항체분자.The monoclonal antibody molecule of claim 3, which is composed of G28-5, or Fv, Fab, F (ab ′) 2 or Fab ′ portion thereof. ATCC HB9110호로 기탁된 하브리도마 세포주, 또는 그 돌연변이체, 재결합체 또는 그 유전공학적 유도체에 의해서 생산된 것이 특징인 제3항의 모노클로날 항체분자.The monoclonal antibody molecule of claim 3, characterized by being produced by a hybridoma cell line deposited with ATCC HB9110, or a mutant, recombinant, or genetic engineering derivative thereof. 제1항에 있어서, 임파액으로 구성된 것이 특징인 배위자.The ligand according to claim 1, which is composed of lymphatic fluid. B-세포 성장인자로 구성된 것이 특징인 제6항의 임파액.Lymphatic fluid of claim 6, characterized by consisting of B-cell growth factors. 제6항에 있어서, 임파액이 어떤 세포의 표면에 존재하는 것이 특징인 배위자.The ligand of claim 6, wherein the lymphatic fluid is present on the surface of a cell. 제1,2 또는 6항에 있어서, 배위자에 결합되는 어떤 화합물로 구성된 것이 특징인 배위자.The ligand of claim 1, 2 or 6, which is composed of any compound that is bound to the ligand. 제9항에 있어서, 배위자에 결합된 화합물이 항증식제로 구성된 것이 특징인 배위자.The ligand of claim 9, wherein the compound bound to the ligand is comprised of an antiproliferative agent. 제9항에 있어서, 배위자에 결합된 화합물이 알킬화제로 구성된 것이 특징인 배위자.The ligand of claim 9, wherein the compound bound to the ligand consists of an alkylating agent. 제9항에 있어서, 배위자에 결합된 화합물이 항대사물로 구성된 것이 특징인 배위자.10. The ligand of claim 9, wherein the compound bound to the ligand consists of anti-metabolites. 제9항에 있어서, 배위자에 결합된 화합물이 항생제로 구성된 것이 특징인 배위자.The ligand of claim 9, wherein the compound bound to the ligand is composed of antibiotics. 제9항에 있어서, 배위자에 결합된 화합물이 빈카 알칼로이드로 구성된 것이 특징인 배위자.The ligand of claim 9, wherein the compound bound to the ligand consists of vinca alkaloids. 제9항에 있어서, 배위자에 결합된 화합물이 효소로 구성된 것이 특징인 배위자.The ligand of claim 9, wherein the compound bound to the ligand consists of an enzyme. 제9항에 있어서, 배위자에 결합된 화합물이 백금 배위결합착염으로 구성된 것이 특징인 배위자.The ligand according to claim 9, wherein the compound bound to the ligand consists of platinum coordination complex salt. 제9항에 있어서, 배위자에 결합된 화합물이 방사성 동위원소로 구성된 것이 특징인 배위자.10. The ligand of claim 9, wherein the compound bound to the ligand consists of a radioisotope. 제9항에 있어서, 배위자에 결합된 화합물이 형광화합물로 구성된 것이 특징인 배위자.The ligand of claim 9, wherein the compound bound to the ligand is composed of a fluorescent compound. 모노클로날 G28-5로 정의되는 Bp50, 즉 50킬로달톤 B-세포 표면항원에 결합하는 것이 특징인 순수한 배위자.Pure ligand, characterized by binding to Bp50, defined as monoclonal G28-5, ie 50 kilodalton B-cell surface antigen. 제19항에 있어서, 항체분자 또는 항체분자의 Fv,Fab,F(ab')2또는 Fab' 부분으로 구성된 것이 특징인 배위자.20. The ligand of claim 19, wherein the ligand consists of an antibody molecule or an Fv, Fab, F (ab ') 2 or Fab' portion of the antibody molecule. 제20항에 있어서, 항체분자가 모노클로날 항체분자 또는 모노클로날 항체분자의 Fv,Fab,F(ab')2또는 Fab' 부분으로 구성된 것이 특징인 배위자.The ligand of claim 20, wherein the antibody molecule comprises a monoclonal antibody molecule or a Fv, Fab, F (ab ') 2 or Fab' portion of a monoclonal antibody molecule. 제19항에 있어서, 임파액으로 구성된 것이 특징인 배위자.20. The ligand of claim 19, consisting of lymphatic fluid. 세포성장인자로 구성된 것이 특징인 제22항의 임파액.The lymphatic fluid of claim 22, characterized by a cell growth factor. 제19,20 또는 22항에 있어서, 배위자에 결합되는 어떤 화합물로 구성된 것이 특징인 배위자.The ligand according to claim 19,20 or 22, characterized in that it consists of any compound which is bound to the ligand. 제24항에 있어서, 배위자에 결합된 화합물이 항증식제로 구성되는 것이 특징인 배위자.The ligand of claim 24, wherein the compound bound to the ligand consists of an antiproliferative agent. 제24항에 있어서, 배위자에 결합된 화합물이 알킬화제로 구성된 것이 특징인 배위자The ligand of claim 24, wherein the compound bound to the ligand consists of an alkylating agent. 제24항에 있어서, 배위자에 결합된 화합물이 항대사물로 구성된 것이 특징인 배위자.The ligand of claim 24, wherein the compound bound to the ligand consists of an anti-metabolite. 제24항에 있어서, 배위자에 결합된 화합물이 항생제로 구성된 것이 특징인 배위자.The ligand of claim 24, wherein the compound bound to the ligand is comprised of an antibiotic. 제24항에 있어서, 배위자에 결합된 화합물이 빈카 알칼로이드로 구성된 것이 특징인 배위자.The ligand of claim 24, wherein the compound bound to the ligand consists of vinca alkaloids. 제24항에 있어서, 배위자에 결합된 화합물이 효소로 구성된 것이 특징인 배위자.The ligand of claim 24, wherein the compound bound to the ligand consists of an enzyme. 제24항에 있어서, 배위자에 결합된 화합물이 백금배위결합착염으로 구성된 것이 특징인 배위자.The ligand of claim 24, wherein the compound bound to the ligand consists of platinum coordination complex salts. 제24항에 있어서, 배위자에 결합된 화합물이 방사능 동위원소로 구성된 것이 특징인 배위자.The ligand of claim 24, wherein the compound bound to the ligand consists of radioactive isotopes. 제24항에 있어서, 배위자에 결합된 화합물이 형광화합물로 구성된 것이 특징인 배위자.The ligand of claim 24, wherein the compound bound to the ligand is composed of a fluorescent compound. 모노클로날 항체 G-28-5로 정의되는 순수한 50킬로달톤 B-세포 표면항원.Pure 50 kilodalton B-cell surface antigen as defined by monoclonal antibody G-28-5. 제34항에 있어서, 폴리펩티드로 구성된 것이 특징인 순수한 50킬로달톤 항원.35. The pure 50 kilodalton antigen of claim 34, consisting of a polypeptide. 활성화된 B-세포가 세포사이클을 방해하여 증식을 촉진시키도록 활성화된 B-세포를 모노클로날항체 G-28-5로 정의되는 Bp50, 즉, 50킬로달톤 B-세포 표면항원에 결합하는 배위자를 적당량 처리함을 특징으로하는 B-세포의 증식을 촉진시키는 방법.A ligand that binds activated B-cells to Bp50, defined as monoclonal antibody G-28-5, ie 50 kilodalton B-cell surface antigen, so that activated B-cells interfere with the cell cycle and promote proliferation. A method for promoting the proliferation of B-cells, characterized in that for treating the appropriate amount. 제36항에 있어서, B-세포가 세포사이클중 G0에서 G1단계로 진행하도록 Bp35, 즉 35킬로달톤 B-세포 표면항원에 결합하는 제2항원을 적당량 처리하여 B-세포를 활성화시킴으로 특징으로 하는 방법.37. The method according to claim 36, wherein the B-cell is activated by treating an appropriate amount of Bp35, ie, a second antigen that binds to 35 kilodalton B-cell surface antigen, to proceed from G 0 to G 1 stage in the cell cycle. How to. 제36항 또는 제37항에 있어서, 생체내에서 수행됨을 특징으로 하는 방법.38. The method of claim 36 or 37, which is performed in vivo. 제36항 또는 제37항에 있어서, 시험관내에서 수행됨을 특징으로 하는 방법.38. The method of claim 36 or 37, which is performed in vitro. 제36항 또는 제37항에 있어서, 배위자가 Bp50 또는 Bp50에 결합하는 항체분자의 Fv,Fab,F(ab')2또는 Fab' 부분에 결합하는 항체분자로 구성됨을 특징으로 하는 방법.38. The method of claim 36 or 37, wherein the ligand consists of an antibody molecule that binds to the Fv, Fab, F (ab ') 2 or Fab' portion of an antibody molecule that binds Bp50 or Bp50. 제36항 또는 제37항에 있어서, 배위자가 Bp50 또는 Bp50에 결합하는 모노클로날항체 분자의 Fv,Fab,F(ab')2또는 Fab' 부분에 결합하는 모노클로날항체 분자로 구성됨을 특징으로 하는 방법.38. The antibody of claim 36 or 37, wherein the ligand consists of a monoclonal antibody molecule that binds to the Fv, Fab, F (ab ') 2 or Fab' moiety of a monoclonal antibody molecule that binds Bp50 or Bp50. How to. 제41항에 있어서, 모노클로날항체 분자가 G28-5, 또는 그의 Fv,Fab,F(ab')2또는 Fab' 부분으로 구성됨을 특징으로 하는 방법.42. The method of claim 41, wherein the monoclonal antibody molecule consists of G28-5, or Fv, Fab, F (ab ') 2 or Fab' portions thereof. 제41항에 있어서, 모노클로날항체가 ATCC HB9110호로 기탁된 하이드리도마 세포주 도는 그의 돌연변이체, 재결합체 또는 유전공학적 유도체에 의해서 생산되는 것이 특징인 방법.42. The method of claim 41, wherein the monoclonal antibody is produced by a hydridoma cell line deposited with ATCC HB9110 or a mutant, recombinant or genetic derivative thereof. 제36항 또는 제37항에 있어서, 배위자가 임파액으로 구성됨을 특징으로 하는 방법.38. The method of claim 36 or 37, wherein the ligand consists of lymphatic fluid. 제44항에 있어서, 임파액이 B-세포 성장인자로 구성됨을 특징으로 하는 방법.45. The method of claim 44, wherein the lymphatic fluid consists of B-cell growth factors. 제44항에 있어서, 임파액이 세포의 표면상에 존재하는 것이 특징인 방법.45. The method of claim 44, wherein the lymphatic fluid is present on the surface of the cell. 제37항에 있어서, 제2배위자가 Bp35에 결합하는 항체분자로 구성됨을 특징으로 하는 방법.The method of claim 37, wherein the second ligand consists of antibody molecules that bind Bp35. 제47항에 있어서, Bp35에 결합하는 항체가 모노클로날항체로 구성됨을 특징으로 하는 방법.48. The method of claim 47, wherein the antibody that binds Bp35 consists of a monoclonal antibody. 제37항에 있어서, 활성화된 B-세포를 Bp35에 결합하는 제2배위자에 의해서 활성화시킨후 약 12시간내에 Bp50에 결합하는 배위자로써 처리하는 것을 특징으로 하는 방법.The method of claim 37, wherein the activated B-cells are treated with a ligand that binds to Bp50 within about 12 hours after activation by a second ligand that binds to Bp35. 항증식제와 커플링반응하고 Bp50에 결합하는 배위자의 효과적인 양을 사용하여 Bp50을 발현하는 세포를 처리함을 특징으로하는 모노클로날항체 G28-5로 정의되는 Bp50, 즉 50킬로달톤 B-세포 표면항체를 발현하는 세포의 증식을 억제하는 방법.Bp50, defined as monoclonal antibody G28-5, i.e., 50 kilodalton B-cells, characterized in that it processes the cells expressing Bp50 using an effective amount of a ligand that binds to Bp50 and couples with the antiproliferative agent. A method of inhibiting proliferation of cells expressing surface antibodies. 제50항에 있어서, Bp50을 발현하는 세포가 B-세포로 구성됨을 특징으로 하는 방법.51. The method of claim 50, wherein the cell expressing Bp50 consists of B-cells. 제50항에 있어서, Bp50을 발현하는 세포가 악성종양세포로 구성됨을 특징으로 하는 방법.51. The method of claim 50, wherein the cell expressing Bp50 consists of malignant tumor cells. 제50항에 있어서, 생체내에서 수행됨을 특징으로 하는 방법.51. The method of claim 50, wherein the method is performed in vivo. 제50항에 있어서, 시험관내에서 수행됨을 특징으로 하는 방법.51. The method of claim 50, wherein the method is performed in vitro. 제50항에 있어서, 배위자가 항체분자 또는 그 항체분자의 Fv,Fab,F(ab')2또는 Fab' 부분으로 구성됨을 특징으로 하는 방법.51. The method of claim 50, wherein the ligand consists of an antibody molecule or the Fv, Fab, F (ab ') 2 or Fab' portion of the antibody molecule. 제55항에 있어서, 항체분자가 모노클로날항체 분자 또는 그 모노클로날 항체분자의 Fv,Fab,F(ab')2또는 Fab' 부분으로 구성됨을 특징으로 하는 방법.56. The method of claim 55, wherein the antibody molecule consists of a monoclonal antibody molecule or a Fv, Fab, F (ab ') 2 or Fab' portion of the monoclonal antibody molecule. 제56항에 있어서, 모노클로날항체가 G28-5, 또는 그의 Fv,Fab,F(ab')2또는 Fab' 부분으로 구성됨을 특징으로 하는 방법.The method of claim 56, wherein the monoclonal antibody consists of G28-5, or Fv, Fab, F (ab ') 2 or Fab' moieties. 제56항에 있어서, 모노클로날항체가 ATCC 제HB9110호로 기탁된 하이브리도마 세포주 또는 그의 돌연변이체, 또는 유전공학적 유도체에 의해서 생산됨을 특징으로 하는 방법.The method of claim 56, wherein the monoclonal antibody is produced by a hybridoma cell line deposited with ATCC HB9110 or a mutant thereof, or a genetic engineering derivative. 제50항에 있어서, 배위자가 임파액으로 구성됨을 특징으로 하는 방법.51. The method of claim 50, wherein the ligand consists of lymphatic fluid. 제59항에 있어서, 임파액이 B-세포 성장인자로 구성됨을 특징으로 하는 방법.60. The method of claim 59, wherein the lymphatic fluid consists of B-cell growth factors. 제50항, 제55항 또는 제59항에 있어서, 항증식제가 알킬화제로 구성됨을 특징으로 하는 방법.60. The method of claim 50, 55 or 59, wherein the antiproliferative agent consists of an alkylating agent. 제50항, 제55항 또는 제59항에 있어서, 항증식제가 항대사제로 구성됨을 특징으로 하는 방법.60. The method of claim 50, 55 or 59, wherein the antiproliferative agent consists of an antimetabolic agent. 제50항, 제55항 또는 제59항에 있어서, 항증식제가 항생제로 구성됨을 특징으로 하는 방법.60. The method of claim 50, 55 or 59, wherein the antiproliferative agent consists of antibiotics. 제50항, 제55항 또는 제59항에 있어서, 항증식제가 빈카 알칼로이드로 구성됨을 특징으로 하는 방법.60. The method of claim 50, 55 or 59, wherein the antiproliferative agent consists of vinca alkaloids. 제50항, 제55항 또는 제59항에 있어서, 항증식제가 효소로 구성됨을 특징으로 하는 방법.60. The method of claim 50, 55 or 59, wherein the antiproliferative agent consists of an enzyme. 제50항, 제55항 또는 제59항에 있어서, 항증식제가 백금배위결합 착염으로 구성됨을 특징으로 하는 방법.60. The method of claim 50, 55 or 59, wherein the antiproliferative agent consists of platinum coordination complex salts. 제50항, 제55항 또는 제59항에 있어서, 항증식제가 방사능 동위원소로 구성됨을 특징으로 하는 방법.60. The method of claim 50, 55 or 59, wherein the antiproliferative agent consists of radioactive isotopes. ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.※ Note: The disclosure is based on the initial application.
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