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公开(公告)号：US20140017788A1
公开(公告)日：2014-01-16
申请号：US13941627
申请日：2013-07-15
IPC分类号： C12N5/0784
CPC分类号： C12N5/0639 , A61K2039/5154 , A61K2039/5156 , A61K2039/5158 , C12N2501/24 , C12N2501/52 , C12N2510/00
摘要： This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-γR) agonist and/or a tumor necrosis factor alpha receptor (TNF-αR) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and/or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g., mRNA or DNA), an agonistic antibody to CD40 receptor or by CD40 ligand polypeptide. The enriched populations can be further modified by the administration of an immunogen to the DC. The DC will take up and process the immunogen on its cell surface.
摘要翻译： 本发明提供了制备和使用免疫刺激细胞增强免疫应答的方法。 本发明提供了一种制备成熟树突状细胞（DCs）的方法，其包括以下顺序步骤：（a）用包含干扰素γ受体（IFN-γR）激动剂的第一信号和/或 肿瘤坏死因子α受体（TNF-αR）激动剂产生信号传导的树突状细胞; 和（b）用包含有效量的CD40激动剂的第二瞬时信号发信号通知所述信号传导的树突状细胞以产生CCR7 +成熟树突状细胞。 本发明还提供了通过本发明的方法制备的富含树枝状细胞的群体。 这种树突细胞具有增强的免疫刺激性能和增加的IL-12分泌和/或降低的IL-10分泌。 可以由编码CD40L的外源多核苷酸（例如mRNA或DNA），CD40受体的激动性抗体或CD40配体多肽翻译的一种或多种多肽来启动CD40信号传导。 可以通过向DC施用免疫原来进一步修饰富集的群体。 DC将占据并处理细胞表面的免疫原。
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公开(公告)号：US20120269832A1
公开(公告)日：2012-10-25
申请号：US12226092
申请日：2007-04-06
IPC分类号： C12N5/0784 , C12N5/10 , A61K35/12 , C12N15/63
CPC分类号： C12N5/0639 , A61K2039/5154 , A61K2039/5156 , A61K2039/5158 , C12N2501/24 , C12N2501/52 , C12N2510/00
摘要： This invention provides novel CD40L polypeptides and nucleic acids, as well as antigen presenting cells and vaccines comprising such CD40L polypeptides and/or nucleic acids, and related methods for preparing the antigen presenting cells and vaccines. The antigen presenting cells and vaccines are useful for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-?R) agonist and/or a tumor necrosis factor alpha receptor (TNF-?R) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and/or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g., mRNA or DNA), an agonistic antibody to CD40 receptor or by CD40 ligand polypeptide. The enriched populations can be further modified by the administration of an immunogen to the DC. The DC will take up and process the immunogen on its cell surface.
摘要翻译： 本发明提供了新的CD40L多肽和核酸，以及包含这种CD40L多肽和/或核酸的抗原呈递细胞和疫苗，以及用于制备抗原呈递细胞和疫苗的相关方法。 抗原呈递细胞和疫苗可用于增强免疫应答。 本发明提供了一种制备成熟树突状细胞（DCs）的方法，其包括以下顺序步骤：（a）用包含干扰素γ受体（IFN-αR）激动剂和/或细胞的第一信号将分离的未成熟树突状细胞（iDC） 肿瘤坏死因子α受体（TNF-αR）激动剂产生信号传导的树突状细胞; 和（b）用包含有效量的CD40激动剂的第二瞬时信号发信号通知所述信号传导的树突状细胞以产生CCR7 +成熟树突状细胞。 本发明还提供了通过本发明的方法制备的富含树枝状细胞的群体。 这种树突细胞具有增强的免疫刺激性能和增加的IL-12分泌和/或降低的IL-10分泌。 可以由编码CD40L的外源多核苷酸（例如mRNA或DNA），CD40受体的激动性抗体或CD40配体多肽翻译的一种或多种多肽来启动CD40信号传导。 可以通过向DC施用免疫原来进一步修饰富集的群体。 DC将占据并处理细胞表面的免疫原。
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公开(公告)号：US20070082400A1
公开(公告)日：2007-04-12
申请号：US11400774
申请日：2006-04-07
CPC分类号： C12N5/0639 , A61K2039/5154 , A61K2039/5156 , A61K2039/5158 , C12N2501/24 , C12N2501/52 , C12N2510/00
摘要： This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-γR) agonist and/or a tumor necrosis factor alpha receptor (TNF-αR) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and/or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g., mRNA or DNA), an agonistic antibody to CD40 receptor or by CD40 ligand polypeptide. The enriched populations can be further modified by the administration of an immunogen to the DC. The DC will take up and process the immunogen on its cell surface.
摘要翻译： 本发明提供了制备和使用免疫刺激细胞增强免疫应答的方法。 本发明提供了一种制备成熟树突状细胞（DCs）的方法，其包括以下顺序步骤：（a）用包含干扰素γ受体（IFN-γR）激动剂的第一信号和/或 肿瘤坏死因子α受体（TNF-αR）激动剂产生信号传导的树突状细胞; 和（b）用包含有效量的CD40激动剂的第二瞬时信号发信号通知所述信号传导的树突状细胞以产生CCR7 +成熟树状细胞。 本发明还提供了通过本发明的方法制备的富含树枝状细胞的群体。 这种树突细胞具有增强的免疫刺激性能和增加的IL-12分泌和/或降低的IL-10分泌。 可以由编码CD40L的外源多核苷酸（例如mRNA或DNA），CD40受体的激动性抗体或CD40配体多肽翻译的一种或多种多肽来启动CD40信号传导。 可以通过向DC施用免疫原来进一步修饰富集的群体。 DC将占据并处理细胞表面的免疫原。
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公开(公告)号：US08822223B2
公开(公告)日：2014-09-02
申请号：US11246387
申请日：2005-10-07
申请人： Don Healey , Irina Tcherepanova , Melissa Adams
发明人： Don Healey , Irina Tcherepanova , Melissa Adams
CPC分类号： C12N5/0639 , A61K2039/5154 , C12N15/87 , C12N2500/36 , C12N2501/02 , C12N2501/22 , C12N2501/23 , C12N2501/24 , C12N2501/52 , C12N2510/00
摘要： This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-γR) agonist and/or a tumor necrosis factor alpha receptor (TNF-αR) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and/or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g., mRNA or DNA), an agonistic antibody to CD40 receptor or by CD40 ligand polypeptide. The enriched populations can be further modified by the administration of an immunogen to the DC. The DC will take up and process the immunogen on its cell surface.
摘要翻译： 本发明提供了制备和使用免疫刺激细胞增强免疫应答的方法。 本发明提供了一种制备成熟树突状细胞（DC）的方法，包括以下顺序的步骤：（a）用包含干扰素γ受体（IFN-γR）激动剂和/或 肿瘤坏死因子α受体（TNF-αR）激动剂产生信号传导的树突状细胞; 和（b）用包含有效量的CD40激动剂的第二瞬时信号发信号通知所述信号传导的树突状细胞以产生CCR7 +成熟树突状细胞。 本发明还提供了通过本发明的方法制备的富含树枝状细胞的群体。 这种树突细胞具有增强的免疫刺激性能和增加的IL-12分泌和/或降低的IL-10分泌。 可以由编码CD40L的外源多核苷酸（例如mRNA或DNA），CD40受体的激动性抗体或CD40配体多肽翻译的一种或多种多肽来启动CD40信号传导。 可以通过向DC施用免疫原来进一步修饰富集的群体。 DC将占据并处理细胞表面的免疫原。
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公开(公告)号：US20060078994A1
公开(公告)日：2006-04-13
申请号：US11246387
申请日：2005-10-07
IPC分类号： C12N5/08
CPC分类号： C12N5/0639 , A61K2039/5154 , C12N15/87 , C12N2500/36 , C12N2501/02 , C12N2501/22 , C12N2501/23 , C12N2501/24 , C12N2501/52 , C12N2510/00
摘要： This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-γR) agonist and/or a tumor necrosis factor alpha receptor (TNF-αR) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and/or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g., mRNA or DNA), an agonistic antibody to CD40 receptor or by CD40 ligand polypeptide. The enriched populations can be further modified by the administration of an immunogen to the DC. The DC will take up and process the immunogen on its cell surface.
摘要翻译： 本发明提供了制备和使用免疫刺激细胞增强免疫应答的方法。 本发明提供了一种制备成熟树突状细胞（DCs）的方法，其包括以下顺序步骤：（a）用包含干扰素γ受体（IFN-γR）激动剂的第一信号和/或 肿瘤坏死因子α受体（TNF-αR）激动剂产生信号传导的树突状细胞; 和（b）用包含有效量的CD40激动剂的第二瞬时信号发信号通知所述信号传导的树突状细胞以产生CCR7 +成熟树状细胞。 本发明还提供了通过本发明的方法制备的富含树枝状细胞的群体。 这种树突细胞具有增强的免疫刺激性能和增加的IL-12分泌和/或降低的IL-10分泌。 可以由编码CD40L的外源多核苷酸（例如mRNA或DNA），CD40受体的激动性抗体或CD40配体多肽翻译的一种或多种多肽来启动CD40信号传导。 可以通过向DC施用免疫原来进一步修饰富集的群体。 DC将占据并处理细胞表面的免疫原。
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公开(公告)号：US20080145931A1
公开(公告)日：2008-06-19
申请号：US11664899
申请日：2005-10-07
IPC分类号： C12N5/02
CPC分类号： C12N5/0639 , A61K2039/5154 , C12N15/87 , C12N2500/36 , C12N2501/02 , C12N2501/22 , C12N2501/23 , C12N2501/24 , C12N2501/52 , C12N2510/00
摘要： This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-γR) agonist and/or a tumor necrosis factor alpha receptor (TNF-αR) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and/or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g., mRNA or DNA), an agonistic antibody to CD40 receptor or by CD40 ligand polypeptide. The enriched populations can be further modified by the administration of an immunogen to the DC. The DC will take up and process the immunogen on its cell surface.
摘要翻译： 本发明提供了制备和使用免疫刺激细胞增强免疫应答的方法。 本发明提供了一种制备成熟树突状细胞（DCs）的方法，其包括以下顺序步骤：（a）用包含干扰素γ受体（IFN-γR）激动剂的第一信号和/或 肿瘤坏死因子α受体（TNF-αR）激动剂产生信号传导的树突状细胞; 和（b）用包含有效量的CD40激动剂的第二瞬时信号发信号通知所述信号传导的树突状细胞以产生CCR7 +成熟树状细胞。 本发明还提供了通过本发明的方法制备的富含树枝状细胞的群体。 这种树突细胞具有增强的免疫刺激性能和增加的IL-12分泌和/或降低的IL-10分泌。 可以由编码CD40L的外源多核苷酸（例如mRNA或DNA），CD40受体的激动性抗体或CD40配体多肽翻译的一种或多种多肽来启动CD40信号传导。 可以通过向DC施用免疫原来进一步修饰富集的群体。 DC将占据并处理细胞表面的免疫原。
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公开(公告)号：US08513008B2
公开(公告)日：2013-08-20
申请号：US11400774
申请日：2006-04-07
申请人： Irina Tcherepanova , Melissa Adams
发明人： Irina Tcherepanova , Melissa Adams
CPC分类号： C12N5/0639 , A61K2039/5154 , A61K2039/5156 , A61K2039/5158 , C12N2501/24 , C12N2501/52 , C12N2510/00
摘要： This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-γR) agonist and/or a tumor necrosis factor alpha receptor (TNF-αR) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and/or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g., mRNA or DNA), an agonistic antibody to CD40 receptor or by CD40 ligand polypeptide. The enriched populations can be further modified by the administration of an immunogen to the DC. The DC will take up and process the immunogen on its cell surface.
摘要翻译： 本发明提供了制备和使用免疫刺激细胞增强免疫应答的方法。 本发明提供了一种制备成熟树突状细胞（DCs）的方法，其包括以下顺序步骤：（a）用包含干扰素γ受体（IFN-γR）激动剂的第一信号和/或 肿瘤坏死因子α受体（TNF-αR）激动剂产生信号传导的树突状细胞; 和（b）用包含有效量的CD40激动剂的第二瞬时信号发信号通知所述信号传导的树突状细胞以产生CCR7 +成熟树突状细胞。 本发明还提供了通过本发明的方法制备的富含树枝状细胞的群体。 这种树突细胞具有增强的免疫刺激性能和增加的IL-12分泌和/或降低的IL-10分泌。 可以由编码CD40L的外源多核苷酸（例如mRNA或DNA），CD40受体的激动性抗体或CD40配体多肽翻译的一种或多种多肽来启动CD40信号传导。 可以通过向DC施用免疫原来进一步修饰富集的群体。 DC将占据并处理细胞表面的免疫原。
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8.发明授权公开(公告)号：US09970068B2
公开(公告)日：2018-05-15
申请号：US13479335
申请日：2012-05-24
申请人： Irina Tcherepanova , Aijing Starr , Brad Lackford
发明人： Irina Tcherepanova , Aijing Starr , Brad Lackford
CPC分类号： C12Q1/703 , C12Q2525/143 , C12Q2521/119
摘要： The invention relates to improved methods and compositions for the nucleic acid amplification of one or multiple variants (strains) of Human Immunodeficiency Virus (HIV) present in a sample, and preferably in a sample from a pathogen infected individual. In particular, novel primers, methods and kits for the amplification of one or more species of HIV Rev, Gag and Nef nucleic acids are provided. The amplified HIV nucleic acid can be used to identify and/or quantitate HIV variants present in a sample. Nucleic acids produced by the methods of the invention or the proteins encoded thereby can also be used directly as vaccines or to transfect/load antigen presenting cells. The loaded antigen presenting cells can be used as a vaccine for the treatment or prevention of HIV infection.
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公开(公告)号：US09085807B2
公开(公告)日：2015-07-21
申请号：US11662828
申请日：2005-09-14
CPC分类号： C07K14/005 , A61K39/21 , A61K2039/5154 , A61K2039/5156 , C12N7/00 , C12N2740/16041 , C12N2740/16234 , C12N2740/16334 , C12Q1/703
摘要： This in invention relates to methods for the nucleic acid amplification of multiple variants (strains) of any pathogen present in a sample, and preferably in a sample from a pathogen infected individual. In preferred embodiments, the pathogen is a retrovirus, such as HIV. The amplified pathogen nucleic acid can be used to identify the pathogen variants present in a sample, to quantitate the pathogen present in a sample, and as a nucleic acid vaccine, or in the preparation of antigen presenting cell vaccines. Nucleic acids produced by the methods of the invention or the proteins encoded thereby can be used to transfect/load antigen presenting cells. The loaded antigen presenting cells can then be used as a vaccine for the treatment of pathogen infection. In another embodiment, nucleic acids produced by the methods of the invention can be used directly as nucleic acid vaccines without prior loading into antigen presenting cells.
摘要翻译： 本发明涉及用于核酸扩增样品中存在的任何病原体的多种变体（菌株）的方法，优选来自病原体感染个体的样品。 在优选的实施方案中，病原体是逆转录病毒，例如HIV。 扩增的病原体核酸可用于鉴定样品中存在的病原体变体，以定量样品中存在的病原体，以及作为核酸疫苗，或用于制备抗原呈递细胞疫苗。 通过本发明的方法产生的核酸或由其编码的蛋白质可用于转染/负载抗原呈递细胞。 然后将负载的抗原呈递细胞用作用于治疗病原体感染的疫苗。 在另一个实施方案中，通过本发明的方法产生的核酸可以直接用作核酸疫苗而不预先加载到抗原呈递细胞中。
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公开(公告)号：US08153425B2
公开(公告)日：2012-04-10
申请号：US11918076
申请日：2006-04-07
IPC分类号： C12N5/0784 , C12N5/00
CPC分类号： C12N5/0639 , A61K2039/5154 , C12N2501/02 , C12N2501/22 , C12N2501/23 , C12N2501/2301 , C12N2501/2304 , C12N2501/2306 , C12N2501/24 , C12N2501/25 , C12N2502/11 , C12N2506/11 , C12N2506/115 , C12N2523/00
摘要： Methods are provided for the production of dendritic cells from monocytes that have been incubated at a temperature of 1° C.-34° C. for a period of approximately 6 to 96 hours from the time they are isolated from a subject. After the incubation period, the monocytes can then be induced to differentiate into dendritic cells. Mature dendritic cells made by the methods of the invention have increased levels of one or more of CD80, CD83, CD86, MHC class I molecules, or MHC class II molecules as compared to mature dendritic cells prepared from monocytes that have not been held at 1° C.-34° C. for at least 6 hours from the time they were isolated from a subject. Dendritic cells made by the methods of the invention are useful for the preparation of vaccines and for the stimulation of T cells.
摘要翻译： 提供了用于从单核细胞生产树突状细胞的方法，其已经在从受试者分离的时间内在1℃-34℃的温度下孵育约6至96小时。 潜伏期后，可诱导单核细胞分化为树突状细胞。 通过本发明的方法制备的成熟树突状细胞与从未保持在1的单核细胞制备的成熟树突状细胞相比，具有增加CD80，CD83，CD86，MHC I类分子或MHC II类分子中的一种或多种的水平 从受试者分离出的时间至少6小时。 通过本发明方法制备的树突状细胞可用于制备疫苗和刺激T细胞。
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