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

IPC分类号： C12N15/87 ,  C12N5/00 ,  C12N5/071 ,  A61K39/00 ,  C12N5/02 ,  A01N63/00 ,  A61K48/00

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。

公开(公告)号：US20140017788A1

公开(公告)日：2014-01-16

申请号：US13941627

申请日：2013-07-15

申请人： Don Healey ,  Irina Tcherepanova ,  Melissa Adams ,  Mark DeBenedette

发明人： Don Healey ,  Irina Tcherepanova ,  Melissa Adams ,  Mark DeBenedette

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。

公开(公告)号：US20060078994A1

公开(公告)日：2006-04-13

申请号：US11246387

申请日：2005-10-07

申请人： Don Healey ,  Irina Tcherepanova ,  Melissa Adams ,  Atsushi Hinohara

发明人： Don Healey ,  Irina Tcherepanova ,  Melissa Adams ,  Atsushi Hinohara

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。

公开(公告)号：US20120269832A1

公开(公告)日：2012-10-25

申请号：US12226092

申请日：2007-04-06

申请人： Donald Healey ,  Irina Tcherepanova ,  Atsushi Hinohara ,  Melissa Adams ,  Mark DeBenedette

发明人： Donald Healey ,  Irina Tcherepanova ,  Atsushi Hinohara ,  Melissa Adams ,  Mark DeBenedette

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。

公开(公告)号：US20070082400A1

公开(公告)日：2007-04-12

申请号：US11400774

申请日：2006-04-07

申请人： Donald Healey ,  Irina Tcherepanova ,  Melissa Adams ,  Atsushi Hinohara ,  Mark DeBenedette

发明人： Donald Healey ,  Irina Tcherepanova ,  Melissa Adams ,  Atsushi Hinohara ,  Mark DeBenedette

IPC分类号： C12N15/87 ,  C12N5/08

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。

公开(公告)号：US20080145931A1

公开(公告)日：2008-06-19

申请号：US11664899

申请日：2005-10-07

申请人： Donald Healey ,  Irina Tcherepanova ,  Atsushi Hinohara ,  Melissa Adams

发明人： Donald Healey ,  Irina Tcherepanova ,  Atsushi Hinohara ,  Melissa Adams

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。

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

IPC分类号： C12N5/00 ,  C12N15/00 ,  C12N5/071 ,  A61K39/00 ,  C12N5/02 ,  A01N63/00 ,  A61K48/00

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。

公开(公告)号：US20060190485A1

公开(公告)日：2006-08-24

申请号：US11063567

申请日：2005-02-24

申请人： Neil Adams ,  Herb Little ,  Melissa Adams

发明人： Neil Adams ,  Herb Little ,  Melissa Adams

IPC分类号： G06F17/00

CPC分类号： G06Q10/109

摘要： The present invention provides a method for notifying at least one invitee of an initial event of changes to the initial event. The method comprises receiving the initial event comprising a plurality of initial event elements and receiving an updated event comprising a plurality of updated event elements, each updated event element corresponding to a respective initial event element. The updated event elements are compared to the initial event elements to determine which of the updated event elements are changed event elements that differ from their respective initial event elements and the at least one invitee is notified of any specific changed event elements.

摘要翻译： 本发明提供一种用于通知至少一个受邀者初始事件的初始改变事件的方法。 该方法包括接收包括多个初始事件元素的初始事件，并且接收包括多个更新的事件元素的更新事件，每个更新的事件元素对应于相应的初始事件元素。 将更新的事件元素与初始事件元素进行比较，以确定哪些更新的事件元素被改变，不同于它们各自的初始事件元素的事件元素，并且向至少一个被请求者通知任何特定改变的事件元素。

公开(公告)号：US08060539B2

公开(公告)日：2011-11-15

申请号：US11063567

申请日：2005-02-24

申请人： Neil Adams ,  Herb Little ,  Melissa Adams

发明人： Neil Adams ,  Herb Little ,  Melissa Adams

IPC分类号： G06F17/30

CPC分类号： G06Q10/109

摘要： The present invention provides a method for notifying at least one invitee of an initial event of changes to the initial event. The method comprises receiving the initial event comprising a plurality of initial event elements and receiving an updated event comprising a plurality of updated event elements, each updated event element corresponding to a respective initial event element. The updated event elements are compared to the initial event elements to determine which of the updated event elements are changed event elements that differ from their respective initial event elements and the at least one invitee is notified of any specific changed event elements.

摘要翻译： 本发明提供一种用于通知至少一个受邀者初始事件的初始改变事件的方法。 该方法包括接收包括多个初始事件元素的初始事件，并且接收包括多个更新的事件元素的更新事件，每个更新的事件元素对应于相应的初始事件元素。 将更新的事件元素与初始事件元素进行比较，以确定哪些更新的事件元素被改变，不同于它们各自的初始事件元素的事件元素，并且向至少一个被请求者通知任何特定改变的事件元素。