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1. 发明授权

US06602709B1 Methods for use of apoptotic cells to deliver antigen to dendritic cells for induction or tolerization of T cells 有权
标题翻译：使用凋亡细胞将抗原递送至树突状细胞以诱导或耐受T细胞的方法
公开(公告)号：US06602709B1
公开(公告)日：2003-08-05
申请号：US09251896
申请日：1999-02-19
申请人： Matthew L. Albert , Nina Bhardwaj , Ralph M. Steinman , Kayo Inaba , Robert Darnell
发明人： Matthew L. Albert , Nina Bhardwaj , Ralph M. Steinman , Kayo Inaba , Robert Darnell
IPC分类号： C12N508
CPC分类号： A61K39/0008 , A61K39/001 , A61K39/12 , A61K39/145 , A61K39/385 , A61K48/00 , A61K2039/5154 , A61K2039/5158 , A61K2039/57 , A61K2039/605 , C12N5/0639 , C12N2501/48 , C12N2760/16134 , Y02A50/412
摘要： This invention relates to methods and compositions useful for delivering antigens to dendritic cells which are then useful for inducing antigen-specific cytotoxic T lymphocytes and T helper cells. This invention also provides assays for evaluating the activity of cytotoxic T lymphocytes. According to the invention, antigens are targeted to dendritic cells by apoptotic cells which may also be modified to express non-native antigens for presentation to the dendritic cells. The dendritic cells which are primed by the apoptotic cells are capable of processing and presenting the processed antigen and inducing cytotoxic T lymphocyte activity or may also be used in vaccine therapies.
摘要翻译：本发明涉及用于将抗原递送至树突状细胞的方法和组合物，其然后可用于诱导抗原特异性细胞毒性T淋巴细胞和T辅助细胞。本发明还提供了用于评估细胞毒性T淋巴细胞活性的测定法。根据本发明，抗原通过凋亡细胞靶向树突细胞，凋亡细胞也可以被修饰以表达非天然抗原以呈递给树突状细胞。由凋亡细胞引发的树突状细胞能够加工和呈递加工的抗原并诱导细胞毒性T淋巴细胞活性，或者也可以用于疫苗疗法。

2. 发明授权

US07989203B2 Methods for use of apoptotic cells to deliver antigen to dendritic cells for induction or tolerization of T cells 有权
标题翻译：使用凋亡细胞将抗原递送至树突状细胞以诱导或耐受T细胞的方法
公开(公告)号：US07989203B2
公开(公告)日：2011-08-02
申请号：US11450972
申请日：2006-06-09
申请人： Matthew L. Albert , Nina Bhardwaj , Ralph M. Steinman , Kayo Inaba , Robert Darnell
发明人： Matthew L. Albert , Nina Bhardwaj , Ralph M. Steinman , Kayo Inaba , Robert Darnell
IPC分类号： C12N5/071
CPC分类号： A61K39/0008 , A61K39/001 , A61K39/12 , A61K39/145 , A61K39/385 , A61K48/00 , A61K2039/5154 , A61K2039/5158 , A61K2039/57 , A61K2039/605 , C12N5/0639 , C12N2501/48 , C12N2760/16134 , Y02A50/412
摘要： This invention relates to methods and compositions useful for delivering antigens to dendritic cells which are then useful for inducing antigen-specific cytotoxic T lymphocytes and T helper cells. This invention also provides assays for evaluating the activity of cytotoxic T lymphocytes. According to the invention, antigens are targeted to dendritic cells by apoptotic cells which may also be modified to express non-native antigens for presentation to the dendritic cells. The dendritic cells which are primed by the apoptotic cells are capable of processing and presenting the processed antigen and inducing cytotoxic T lymphocyte activity or may also be used in vaccine therapies.
摘要翻译：本发明涉及用于将抗原递送至树突状细胞的方法和组合物，其然后可用于诱导抗原特异性细胞毒性T淋巴细胞和T辅助细胞。本发明还提供了用于评估细胞毒性T淋巴细胞活性的测定法。根据本发明，抗原通过凋亡细胞靶向树突细胞，凋亡细胞也可以被修饰以表达非天然抗原以呈递给树突状细胞。由凋亡细胞引发的树突状细胞能够加工和呈递加工的抗原并诱导细胞毒性T淋巴细胞活性，或者也可以用于疫苗疗法。

3. 发明授权

US07129037B2 Methods for use of apoptotic cells to deliver antigen to dendritic cells for induction or tolerization of T cells 有权
公开(公告)号：US07129037B2
公开(公告)日：2006-10-31
申请号：US10014877
申请日：2001-12-11
申请人： Matthew L. Albert , Nina Bhardwaj , Ralph M. Steinman , Kayo Inaba , Robert Darnell
发明人： Matthew L. Albert , Nina Bhardwaj , Ralph M. Steinman , Kayo Inaba , Robert Darnell
IPC分类号： C12Q1/00 , G01N33/53 , C12N5/08 , C12N5/00
CPC分类号： A61K39/0008 , A61K39/001 , A61K39/12 , A61K39/145 , A61K39/385 , A61K48/00 , A61K2039/5154 , A61K2039/5158 , A61K2039/57 , A61K2039/605 , C12N5/0639 , C12N2501/48 , C12N2760/16134 , Y02A50/412
摘要： This invention relates to methods and compositions useful for delivering antigens to dendritic cells which are then useful for inducing antigen-specific cytotoxic T lymphocytes and T helper cells. This invention also provides assays for evaluating the activity of cytotoxic T lymphocytes. According to the invention, antigens are targeted to dendritic cells by apoptotic cells which may also be modified to express non-native antigens for presentation to the dendritic cells. The dendritic cells which are primed by the apoptotic cells are capable of processing and presenting the processed antigen and inducing cytotoxic T lymphocyte activity or may also be used in vaccine therapies.

4. 发明授权

US06300090B1 Methods of use of viral vectors to deliver antigen to dendritic cells 失效
标题翻译：使用病毒载体将抗原递送至树突状细胞的方法
公开(公告)号：US06300090B1
公开(公告)日：2001-10-09
申请号：US08693586
申请日：1996-08-01
申请人： Ralph M. Steinman , Nina Bhardwaj
发明人： Ralph M. Steinman , Nina Bhardwaj
IPC分类号： G01N3353
CPC分类号： C12N7/00 , A61K39/00 , A61K39/12 , A61K39/145 , A61K2039/5154 , A61K2039/5252 , A61K2039/5254 , A61K2039/57 , C12N15/86 , C12N2760/16043 , C12N2760/16122 , C12N2760/16134 , C12N2760/16143 , C12N2760/16161 , Y02A50/412
摘要： This invention relates to methods and compositions useful for delivering antigens to dendritic cells which are then useful for inducing T antigen specific cytotoxic T lymphocytes. This invention also provides assays for evaluating the activity of cytotoxic T lymphocytes. According to the invention, antigens are provided to dendritic cells using a viral vector such as influenza virus which may be modified to express non-native antigens for presentation to the dendritic cells. The dendritic cells which are infected with the vector are then capable of presenting the antigen and inducing cytotoxic T lymphocyte activity or may also be used as vaccines.
摘要翻译：本发明涉及用于将抗原递送至树突状细胞的方法和组合物，其然后可用于诱导T抗原特异性细胞毒性T淋巴细胞。本发明还提供了用于评估细胞毒性T淋巴细胞活性的测定法。根据本发明，使用病毒载体如流感病毒将抗原提供给树突状细胞，所述病毒载体可被修饰以表达非天然抗原以呈递至树突状细胞。然后用载体感染的树突状细胞能够呈递抗原并诱导细胞毒性T淋巴细胞活性，或者也可以用作疫苗。

5. 发明授权

US5851756A Method for in vitro proliferation of dendritic cell precursors and their use to produce immunogens 失效
公开(公告)号：US5851756A
公开(公告)日：1998-12-22
申请号：US458230
申请日：1995-06-02
申请人： Ralph M. Steinman , Kayo Inaba , Gerold Schuler
发明人： Ralph M. Steinman , Kayo Inaba , Gerold Schuler
IPC分类号： C12N5/10 , A61K35/12 , A61K39/00 , A61P37/00 , C07K14/35 , C12N5/02 , C12N5/0784 , C12N5/00 , C12N5/08 , A01N1/02
CPC分类号： C12N5/0639 , A61K39/0008 , A61K2035/122 , A61K2039/5154 , C12N2501/22 , C12N2501/23 , C12N2501/25
摘要： A method for producing proliferating cultures of dendritic cell precursors is provided. Also provided is a method for producing mature dendritic cells in culture from the proliferating dendritic cell precursors. The cultures of mature dendritic cells provide an effective means of producing novel T cell dependent antigens comprised of dendritic cell modified antigens or dendritic cells pulsed with antigen, including particulates, which antigen is processed and expressed on the antigen-activated dendritic cell. The novel antigens of the invention may be used as immunogens for vaccines or for the treatment of disease. These antigens may also be used to treat autoimmune diseases such as juvenile diabetes and multiple sclerosis.

6. 发明授权

US06455299B1 Methods of use of viral vectors to deliver antigen to dendritic cells 有权
标题翻译：使用病毒载体将抗原递送至树突状细胞的方法
公开(公告)号：US06455299B1
公开(公告)日：2002-09-24
申请号：US09310560
申请日：1999-05-12
申请人： Ralph M. Steinman , Nina Bhardwaj
发明人： Ralph M. Steinman , Nina Bhardwaj
IPC分类号： C12N700
CPC分类号： C12N7/00 , A61K39/00 , A61K39/12 , A61K39/145 , A61K2039/5154 , A61K2039/5252 , A61K2039/5254 , A61K2039/57 , C12N15/86 , C12N2760/16043 , C12N2760/16122 , C12N2760/16134 , C12N2760/16143 , C12N2760/16161 , Y02A50/412
摘要： This invention relates to methods and compositions useful for delivering antigens to dendritic cells which are then useful for inducing T antigen specific cytotoxic T lymphocytes. This invention also provides assays for evaluating the activity of cytotoxic T lymphocytes. According to the invention, antigens are provided to dendritic cells using a viral vector such as influenza virus which may be modified to express non-native antigens for presentation to the dendritic cells. The dendritic cells which are infected with the vector are then capable of presenting the antigen and inducing cytotoxic T lymphocyte activity or may also be used as vaccines.
摘要翻译：本发明涉及用于将抗原递送至树突状细胞的方法和组合物，其然后可用于诱导T抗原特异性细胞毒性T淋巴细胞。本发明还提供了用于评估细胞毒性T淋巴细胞活性的测定法。根据本发明，使用病毒载体如流感病毒将抗原提供给树突状细胞，所述病毒载体可被修饰以表达非天然抗原以呈递至树突状细胞。然后用载体感染的树突状细胞能够呈递抗原并诱导细胞毒性T淋巴细胞活性，或者也可以用作疫苗。

7. 发明申请

US20090029469A1 Method for in vitro proliferation of dendritic cell precursors and their use to produce immunogens 失效
标题翻译：树突细胞前体的体外增殖方法及其产生免疫原的用途
公开(公告)号：US20090029469A1
公开(公告)日：2009-01-29
申请号：US12218899
申请日：2008-07-17
申请人： Ralph M. Steinman , Kayo Inaba , Gerold Schuler
发明人： Ralph M. Steinman , Kayo Inaba , Gerold Schuler
IPC分类号： C12N5/00
CPC分类号： C12N5/0639 , A61K39/0008 , A61K2035/122 , A61K2039/5154 , C12N2501/22 , C12N2501/23 , C12N2501/25
摘要： A method for producing proliferating cultures of dendritic cell precursors is provided. Also provided is a method for producing mature dendritic cells in culture from the proliferating dendritic cell precursors. The cultures of mature dendritic cells provide an effective means of producing novel T cell dependent antigens comprised of dendritic cell modified antigens or dendritic cells pulsed with antigen, including particulates, which antigen is processed and expressed on the antigen-activated dendritic cell. The novel antigens of the invention may be used as immunogens for vaccines or for the treatment of disease. These antigens may also be used to treat autoimmune diseases such as juvenile diabetes and multiple sclerosis.
摘要翻译：提供了一种用于产生树突状细胞前体的增殖培养物的方法。还提供了从增殖型树突状细胞前体在培养物中产生成熟树突状细胞的方法。成熟树突细胞的培养提供了产生由树突状细胞修饰抗原或用抗原脉冲的树突状细胞的新型T细胞依赖性抗原的有效手段，包括微粒，该抗原在抗原活化的树突状细胞上被加工和表达。本发明的新型抗原可以用作疫苗的免疫原或用于治疗疾病。这些抗原也可用于治疗自身免疫性疾病，例如幼年型糖尿病和多发性硬化症。

8. 发明授权

US07659119B2 Method and compositions for obtaining mature dendritic cells 失效
标题翻译：用于获得成熟树突状细胞的方法和组合物
公开(公告)号：US07659119B2
公开(公告)日：2010-02-09
申请号：US08600483
申请日：1996-02-12
申请人： Ralph M. Steinman , Nina Bhardwaj , Gerold Schuler
发明人： Ralph M. Steinman , Nina Bhardwaj , Gerold Schuler
IPC分类号： C12N5/02
CPC分类号： C12N5/0639 , A61K38/00 , A61K2039/5154 , C12N2501/22 , C12N2501/23 , C12N2502/11
摘要： We describe an improved method for generating sizable numbers of mature dendritic cells from nonproliferating progenitors in human blood. The first step or “priming” phase is a culture of T cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4 to produce immature dendritic cells. The second step or “differentiation” phase requires the exposure to dendritic cell maturation factor such as monocyte conditioned medium. Using this two-step approach, substantial yields are obtained. The dendritic cells derive from this method have all the features of mature cells. They include a stellate cell shape, nonadherence to plastic, and very strong T cell stimulatory activity. The mature dendritic cells produced according to this invention are useful for activating T cells.
摘要翻译：我们描述了一种用于从人血液中的非增殖祖细胞产生大量成熟树突状细胞的改进方法。第一步或“引发”阶段是补充有GM-CSF和IL-4的培养基中产生未成熟树突状细胞的T细胞耗尽的单核细胞的培养物。第二步或“分化”阶段需要暴露于树突状细胞成熟因子如单核细胞条件培养基。使用这种两步法，可以获得显着的产量。这种方法得到的树突状细胞具有成熟细胞的所有特征。它们包括星状细胞形状，不粘附于塑料，以及非常强的T细胞刺激活性。根据本发明产生的成熟树突状细胞可用于激活T细胞。

9. 发明申请

US20090175890A1 USE OF IMMATURE DENDRITIC CELLS TO SILENCE ANTIGEN SPECIFIC CD8+ T CELL FUNCTION 审中-公开
标题翻译：使用轻度的DENDRITIC细胞沉默抗原特异性CD8 + T细胞功能
公开(公告)号：US20090175890A1
公开(公告)日：2009-07-09
申请号：US12346285
申请日：2008-12-30
申请人： Madhav V. Dhodapkar , Ralph M. Steinman , Nina Bhardwaj
发明人： Madhav V. Dhodapkar , Ralph M. Steinman , Nina Bhardwaj
IPC分类号： A61K39/00 , A61K35/12
CPC分类号： A61K39/0008 , A61K2035/122 , A61K2039/5154 , A61K2039/57
摘要： This invention provides methods for silencing a pre-existing immune response in a mammal, as for example, in the setting of autoimmune diseases. The method comprises administering to a mammal immature dendritic cells which have been contacted in vitro with an antigen, or to target the antigen to immature dendritic cells in vivo, in order to silence and/or suppress a pre-existing CD8+ T cell immune response and induce IL-10 producing CD8+ T cells in said mammal. This invention further relates to methods for propagating immature dendritic cells, for maintaining immaturity by modification ex vivo, and uses thereof, including generation of regulatory T cells for passive immunotherapy. The present invention also relates to compositions and kits comprising immature dendritic cells and antigens.
摘要翻译：本发明提供了在哺乳动物中沉默预先存在的免疫应答的方法，例如在自身免疫疾病的设定中。该方法包括向体外施用已经在体外与抗原接触的未成熟树突状细胞或者将抗原靶向体内未成熟树突状细胞，以沉默和/或抑制预先存在的CD8 + T细胞免疫应答和诱导所述哺乳动物中产生IL-10的CD8 + T细胞。本发明还涉及用于通过离体修饰保持不成熟的未成熟树突细胞的方法及其用途，包括产生用于被动免疫治疗的调节性T细胞。本发明还涉及包含未成熟树突状细胞和抗原的组合物和试剂盒。

10. 发明授权

US07198948B2 Methods and compositions for obtaining mature dendritic cells 有权
标题翻译：获得成熟树突状细胞的方法和组合物
公开(公告)号：US07198948B2
公开(公告)日：2007-04-03
申请号：US10047072
申请日：2002-01-15
申请人： Ralph M. Steinman , Nina Bhardwaj , Gerold Schuler
发明人： Ralph M. Steinman , Nina Bhardwaj , Gerold Schuler
IPC分类号： C12N5/02
CPC分类号： C12N5/0639 , A61K38/00 , A61K2039/5154 , C12N2501/22 , C12N2501/23 , C12N2502/11
摘要： We describe an improved method for generating sizable numbers of mature dendritic cells from nonproliferating progenitors in human blood. The first step or “priming” phase is a culture of T cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4 to produce immature dendritic cells. The second step or “differentiation” phase requires the exposure to dendritic cell maturation factor such as monocyte conditioned medium. Using this two-step approach, substantial yields are obtained. The dendritic cells derive from this method have all the features of mature cells. They include a stellate cell shape, nonadherence to plastic, and very strong T cell stimulatory activity. The mature dendritic cells produced according to this invention are useful for activating T cells.
摘要翻译：我们描述了一种用于从人血液中的非增殖祖细胞产生大量成熟树突状细胞的改进方法。第一步或“引发”阶段是补充有GM-CSF和IL-4的培养基中产生未成熟树突状细胞的T细胞耗尽的单核细胞的培养物。第二步或“分化”阶段需要暴露于树突状细胞成熟因子如单核细胞条件培养基。使用这种两步法，可以获得显着的产量。这种方法得到的树突状细胞具有成熟细胞的所有特征。它们包括星状细胞形状，不粘附于塑料，以及非常强的T细胞刺激活性。根据本发明产生的成熟树突状细胞可用于激活T细胞。

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