公开(公告)号：US20100105135A1

公开(公告)日：2010-04-29

申请号：US12609060

申请日：2009-10-30

申请人： Donald DRAKE, III ,  David MOE ,  Conan LI ,  Heather FAHLENKAMP ,  Guzman SANCHEZ-SCHMITZ ,  Russell HIGBEE ,  Robert PARKHILL ,  William L. WARREN

发明人： Donald DRAKE, III ,  David MOE ,  Conan LI ,  Heather FAHLENKAMP ,  Guzman SANCHEZ-SCHMITZ ,  Russell HIGBEE ,  Robert PARKHILL ,  William L. WARREN

IPC分类号： C12N5/0784

CPC分类号： C12N5/0639 ,  C12M23/12 ,  C12M23/20 ,  C12M25/02 ,  C12M25/14 ,  C12N2502/28 ,  C12N2503/00

摘要： Dendritic cells (DCs) for research and clinical applications are typically derived from purified blood monocytes that are cultured in a cocktail of cytokines for a week or more. Because it has been suggested that these cytokine-derived DCs may be deficient in some important immunological functions and might not accurately represent antigen-presenting cell (APC) populations found under physiologic conditions, there is a need for methods that allow the generation of DCs in a more physiologically relevant manner. The present invention comprises a simple and reliable technique for generating large numbers of highly purified DCs, based on a single migration of blood monocytes through endothelial cells that are cultured in, for example, a Transwell® device. The resultant APCs, harvested from the lower Transwell® chamber, resemble other in vitro-generated DC populations in their expression of major histocompatibility (MHC) and costimulatory molecules, ability to phagocytose foreign antigens, and capacity to trigger antigen-specific T cell responses.

摘要翻译： 用于研究和临床应用的树突状细胞（DC）通常衍生自在细胞因子混合物中培养一周或更长时间的纯化血液单核细胞。 由于已经提出这些细胞因子衍生的DC可能在一些重要的免疫功能上有缺陷，并且可能不能准确地代表在生理条件下发现的抗原呈递细胞（APC）群体，所以需要一种允许在 更生理相关的方式。 本发明包括一种用于产生大量高度纯化的DC的简单且可靠的技术，其基于通过在例如Transwell装置中培养的内皮细胞的血液单核细胞的单次迁移。 从下部Transwell室获取的所得APC类似于其主要组织相容性（MHC）和共刺激分子的表达的其他体外产生的DC群体，吞噬外来抗原的能力和触发抗原特异性T细胞应答的能力。

公开(公告)号：US20100178676A1

公开(公告)日：2010-07-15

申请号：US12730899

申请日：2010-03-24

申请人： William L. WARREN ,  Robert PARKHILL ,  Michael N. NGUYEN ,  Guzman SANCHEZ-SCHMITZ ,  Heather FAHLENKAMP ,  Russell HIGBEE ,  Donald DRAKE, III ,  Anatoly KACHURIN ,  David MOE

发明人： William L. WARREN ,  Robert PARKHILL ,  Michael N. NGUYEN ,  Guzman SANCHEZ-SCHMITZ ,  Heather FAHLENKAMP ,  Russell HIGBEE ,  Donald DRAKE, III ,  Anatoly KACHURIN ,  David MOE

IPC分类号： C12P21/00

CPC分类号： C12N5/0697 ,  B01L3/5027 ,  C12N2501/21 ,  C12N2502/094 ,  C12N2502/11 ,  C12N2502/1107 ,  C12N2502/1114 ,  C12N2502/1121 ,  C12N2502/1192 ,  C12N2502/28 ,  C12N2503/02 ,  C12N2503/04 ,  C12N2531/00 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2535/10 ,  G01N33/5082 ,  G01N33/5088

摘要： The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system.

摘要翻译： 本发明涉及构建综合人造免疫系统的方法，其包括适当的体外细胞和组织构建体或其等同物以模拟与哺乳动物中的疫苗相互作用的正常组织。 人造免疫系统可用于测试疫苗候选物在体外的功效，因此可用于加速疫苗开发和测试与免疫系统的药物和化学相互作用。

公开(公告)号：US20110250620A1

公开(公告)日：2011-10-13

申请号：US13167115

申请日：2011-06-23

申请人： Selva SUKUMAR ,  Mohey Eldin M. EL SHIKH ,  John G. TEW ,  Guzman SANCHEZ-SCHMITZ ,  Donald DRAKE, III ,  Luis MOSQUERA ,  Eric MISHKIN ,  Anatoly M. KACHURIN ,  Russell HIGBEE ,  Conan LI ,  William L. WARREN ,  Heather FAHLENKAMP

发明人： Selva SUKUMAR ,  Mohey Eldin M. EL SHIKH ,  John G. TEW ,  Guzman SANCHEZ-SCHMITZ ,  Donald DRAKE, III ,  Luis MOSQUERA ,  Eric MISHKIN ,  Anatoly M. KACHURIN ,  Russell HIGBEE ,  Conan LI ,  William L. WARREN ,  Heather FAHLENKAMP

IPC分类号： G01N33/53

CPC分类号： C07K16/44 ,  C12N5/0639 ,  C12N5/0651 ,  C12N5/0697 ,  C12N2501/052 ,  C12N2501/21 ,  C12N2501/2304 ,  C12N2502/11 ,  C12N2502/1107 ,  C12N2502/1114 ,  C12N2502/1121 ,  C12N2502/1192 ,  C12N2502/28 ,  C12N2503/04 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2533/92 ,  C12N2535/10 ,  G01N33/5047 ,  G01N33/5076 ,  G01N33/5088

摘要： The present invention incorporates germinal centers (GCs) into three-dimensional (3D) engineered tissue constructs (ETCs). In an embodiment, we have incorporated the GC in the design of an artificial immune system (AIS) to examine immune responses to vaccines and other compounds. Development of an in vitro GC adds functionality to an AIS, in that it enables generation of an in vitro human humoral response by human B lymphocytes that is accurate and reproducible, without using human subjects. The invention also permits evaluation of, for example, vaccines, allergens, and immunogens, and activation of human B cells specific for a given antigen, which can then be used to generate human antibodies. In an embodiment of the present invention the function of the in vitro GC is enhanced by placing FDCs and other immune cells in a 3D ETC; FDCs appear more effective over a longer time (antibody production is sustained for up to about 14 days.

摘要翻译： 本发明将生发中心（GC）纳入三维（3D）工程组织构建体（ETC）中。 在一个实施方案中，我们已经将GC并入人造免疫系统（AIS）的设计中，以检查对疫苗和其他化合物的免疫应答。 体外GC的开发为AIS增加了功能，因为它能够在不使用人类受试者的情况下产生准确和可重复的人B淋巴细胞的体外人体液反应。 本发明还允许评估例如疫苗，过敏原和免疫原，以及对给定抗原特异性的人B细胞的活化，然后可以将其用于产生人抗体。 在本发明的一个实施方案中，通过将FDC和其他免疫细胞放置在3D ETC中来增强体外GC的功能; FDC在更长时间内看起来更有效（抗体产生持续长达约14天。

公开(公告)号：US20100184148A1

公开(公告)日：2010-07-22

申请号：US12707563

申请日：2010-02-17

申请人： Selva SUKUMAR ,  Mohey Eldin M. EL SHIKH ,  John G. TEW ,  Guzman SANCHEZ-SCHMITZ ,  Donald DRAKE, III ,  Luis MOSQUERA ,  Eric MISHKIN ,  Anatoly M. KACHURIN ,  Russell HIGBEE ,  Conan LI ,  William L. WARREN ,  Heather FAHLENKAMP

发明人： Selva SUKUMAR ,  Mohey Eldin M. EL SHIKH ,  John G. TEW ,  Guzman SANCHEZ-SCHMITZ ,  Donald DRAKE, III ,  Luis MOSQUERA ,  Eric MISHKIN ,  Anatoly M. KACHURIN ,  Russell HIGBEE ,  Conan LI ,  William L. WARREN ,  Heather FAHLENKAMP

IPC分类号： C12P21/00 ,  C12N5/0781 ,  C12N5/0783

CPC分类号： C07K16/44 ,  C12N5/0639 ,  C12N5/0651 ,  C12N5/0697 ,  C12N2501/052 ,  C12N2501/21 ,  C12N2501/2304 ,  C12N2502/11 ,  C12N2502/1107 ,  C12N2502/1114 ,  C12N2502/1121 ,  C12N2502/1192 ,  C12N2502/28 ,  C12N2503/04 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2533/92 ,  C12N2535/10 ,  G01N33/5047 ,  G01N33/5076 ,  G01N33/5088

摘要： The present invention incorporates germinal centers (GCs) into three-dimensional (3D) engineered tissue constructs (ETCs). In an embodiment, we have incorporated the GC in the design of an artificial immune system (AIS) to examine immune responses to vaccines and other compounds. Development of an in vitro GC adds functionality to an AIS, in that it enables generation of an in vitro human humoral response by human B lymphocytes that is accurate and reproducible, without using human subjects. The invention also permits evaluation of, for example, vaccines, allergens, and immunogens, and activation of human B cells specific for a given antigen, which can then be used to generate human antibodies. In an embodiment of the present invention the function of the in vitro GC is enhanced by placing FDCs and other immune cells in a 3D ETC; FDCs appear more effective over a longer time (antibody production is sustained for up to about 14 days.

摘要翻译： 本发明将生发中心（GC）纳入三维（3D）工程组织构建体（ETC）中。 在一个实施方案中，我们已经将GC并入人造免疫系统（AIS）的设计中，以检查对疫苗和其他化合物的免疫应答。 体外GC的开发为AIS增加了功能，因为它能够在不使用人类受试者的情况下产生准确和可重复的人B淋巴细胞的体外人体液反应。 本发明还允许评估例如疫苗，过敏原和免疫原，以及对给定抗原特异性的人B细胞的活化，然后可以将其用于产生人抗体。 在本发明的一个实施方案中，通过将FDC和其他免疫细胞放置在3D ETC中来增强体外GC的功能; FDC在更长时间内看起来更有效（抗体产生持续长达约14天。

公开(公告)号：US20110269176A1

公开(公告)日：2011-11-03

申请号：US13167131

申请日：2011-06-23

申请人： Selva SUKUMAR ,  Mohey Eldin M. EL SHIKH ,  John G. TEW ,  Guzman SANCHEZ-SCHMITZ ,  Donald DRAKE, III ,  Luis MOSQUERA ,  Eric MISHKIN ,  Anatoly M. KACHURIN ,  Russell HIGBEE ,  Conan LI ,  William L. WARREN ,  Heather FAHLENKAMP

发明人： Selva SUKUMAR ,  Mohey Eldin M. EL SHIKH ,  John G. TEW ,  Guzman SANCHEZ-SCHMITZ ,  Donald DRAKE, III ,  Luis MOSQUERA ,  Eric MISHKIN ,  Anatoly M. KACHURIN ,  Russell HIGBEE ,  Conan LI ,  William L. WARREN ,  Heather FAHLENKAMP

IPC分类号： C12Q1/18

CPC分类号： C07K16/44 ,  C12N5/0639 ,  C12N5/0651 ,  C12N5/0697 ,  C12N2501/052 ,  C12N2501/21 ,  C12N2501/2304 ,  C12N2502/11 ,  C12N2502/1107 ,  C12N2502/1114 ,  C12N2502/1121 ,  C12N2502/1192 ,  C12N2502/28 ,  C12N2503/04 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2533/92 ,  C12N2535/10 ,  G01N33/5047 ,  G01N33/5076 ,  G01N33/5088

摘要： The present invention incorporates germinal centers (GCs) into three-dimensional (3D) engineered tissue constructs (ETCs). In an embodiment, we have incorporated the GC in the design of an artificial immune system (AIS) to examine immune responses to vaccines and other compounds. Development of an in vitro GC adds functionality to an AIS, in that it enables generation of an in vitro human humoral response by human B lymphocytes that is accurate and reproducible, without using human subjects. The invention also permits evaluation of, for example, vaccines, allergens, and immunogens, and activation of human B cells specific for a given antigen, which can then be used to generate human antibodies. In an embodiment of the present invention the function of the in vitro GC is enhanced by placing FDCs and other immune cells in a 3D ETC; FDCs appear more effective over a longer time (antibody production is sustained for up to about 14 days.

摘要翻译： 本发明将生发中心（GC）纳入三维（3D）工程组织构建体（ETC）中。 在一个实施方案中，我们已经将GC并入人造免疫系统（AIS）的设计中，以检查对疫苗和其他化合物的免疫应答。 体外GC的开发为AIS增加了功能，因为它能够在不使用人类受试者的情况下产生准确和可重复的人B淋巴细胞的体外人体液反应。 本发明还允许评估例如疫苗，过敏原和免疫原，以及对给定抗原特异性的人B细胞的活化，然后可以将其用于产生人抗体。 在本发明的一个实施方案中，通过将FDC和其他免疫细胞放置在3D ETC中来增强体外GC的功能; FDC在更长时间内看起来更有效（抗体产生持续长达约14天。

公开(公告)号：US20130078656A1

公开(公告)日：2013-03-28

申请号：US13608579

申请日：2012-09-10

申请人： William L. WARREN ,  Heather FAHLENKAMP ,  Russell HIGBEE ,  Anatoly KACHURIN ,  Conan LI ,  Mike NGUYEN ,  Robert PARKHILL ,  Guzman SANCHEZ-SCHMITZ ,  Darrell J. IRVINE ,  Gwendalyn J. RANDOLPH ,  Nir HACOHEN ,  Bruce TORBETT

发明人： William L. WARREN ,  Heather FAHLENKAMP ,  Russell HIGBEE ,  Anatoly KACHURIN ,  Conan LI ,  Mike NGUYEN ,  Robert PARKHILL ,  Guzman SANCHEZ-SCHMITZ ,  Darrell J. IRVINE ,  Gwendalyn J. RANDOLPH ,  Nir HACOHEN ,  Bruce TORBETT

IPC分类号： C12N5/071

CPC分类号： G01N33/5008 ,  C12N5/0697 ,  C12N5/0698 ,  C12N2501/21 ,  C12N2502/094 ,  C12N2502/11 ,  C12N2502/1107 ,  C12N2502/1114 ,  C12N2502/1121 ,  C12N2502/1157 ,  C12N2502/1192 ,  C12N2502/1323 ,  C12N2502/28 ,  C12N2503/04 ,  C12N2513/00 ,  C12N2531/00 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2535/10 ,  G01N33/5088 ,  G01N2500/10

摘要： The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interaction with the immune system.

摘要翻译： 本发明涉及构建综合人造免疫系统的方法，其包括适当的体外细胞和组织构建体或其等同物以模拟与哺乳动物中的疫苗相互作用的正常组织。 人工免疫系统可用于测试疫苗候选物在体外的功效，因此可用于加速疫苗开发和测试与免疫系统的药物和化学相互作用。

公开(公告)号：US20100159443A1

公开(公告)日：2010-06-24

申请号：US12718084

申请日：2010-03-05

申请人： William L. WARREN ,  Russell HIGBEE ,  Eric MISHKIN ,  Guzman SANCHEZ-SCHMITZ ,  Heather FAHLENKAMP ,  Michael RIVARD

发明人： William L. WARREN ,  Russell HIGBEE ,  Eric MISHKIN ,  Guzman SANCHEZ-SCHMITZ ,  Heather FAHLENKAMP ,  Michael RIVARD

IPC分类号： C12Q1/70 ,  C12Q1/02

CPC分类号： C12M21/08 ,  C12M25/14 ,  C12M35/08 ,  C12N5/0697 ,  C12N2501/21 ,  C12N2502/091 ,  C12N2502/094 ,  C12N2502/11 ,  C12N2502/28 ,  C12N2502/30 ,  C12N2503/04 ,  C12N2531/00 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2535/10 ,  G01N33/5044 ,  G01N33/5064 ,  G01N33/5082 ,  G01N33/5088 ,  G01N2800/24

摘要： The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising a three-dimensional matrix comprising lymphoid tissue, a three-dimensional matrix comprising epithelial and/or endothelial cells, and diseased cells. The artificial immune system of the present invention can be used for in vitro testing of vaccines, adjuvants, immunotherapy candidates, cosmetics, drugs, biologics and other chemicals.

摘要翻译： 本发明涉及人造免疫系统的制备方法。 人造免疫系统包括细胞培养物，其包含包含淋巴组织的三维基质，包含上皮和/或内皮细胞的三维基质和患病细胞。 本发明的人造免疫系统可用于疫苗，佐剂，免疫治疗候选物，化妆品，药​​物，生物制剂和其它化学品的体外试验。

公开(公告)号：US20090011455A1

公开(公告)日：2009-01-08

申请号：US12047107

申请日：2008-03-12

申请人： William L. WARREN ,  Heather FAHLENKAMP ,  Russell G. HIGBEE ,  Eric M. MISHKIN ,  Guzman SANCHEZ-SCHMITZ ,  Michael D. RIVARD ,  Santosh PAWAR

发明人： William L. WARREN ,  Heather FAHLENKAMP ,  Russell G. HIGBEE ,  Eric M. MISHKIN ,  Guzman SANCHEZ-SCHMITZ ,  Michael D. RIVARD ,  Santosh PAWAR

IPC分类号： C12Q1/02 ,  C12N5/06

CPC分类号： C12M21/08 ,  C12M25/14 ,  C12M35/08 ,  C12N5/0651 ,  C12N5/0698 ,  C12N2501/21 ,  C12N2502/091 ,  C12N2502/094 ,  C12N2502/11 ,  C12N2502/1192 ,  C12N2502/1323 ,  C12N2502/28 ,  C12N2502/30 ,  C12N2503/04 ,  C12N2531/00 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2535/10 ,  G01N33/5044 ,  G01N33/5064 ,  G01N33/5082 ,  G01N33/5088 ,  G01N2800/24

摘要： The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the tissues of the immune system in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates and other materials in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system, coupled with disease models to provide a more complete representation of an immune response.

摘要翻译： 本发明涉及构建综合人造免疫系统的方法，其包括适当的体外细胞和组织构建体或其等同物以模拟哺乳动物免疫系统的组织。 人造免疫系统可用于测试疫苗候选物和其他材料在体外的功效，因此，有助于加速疫苗开发和测试与免疫系统的药物和化学相互作用，加上疾病模型，以提供更完整的表示 免疫反应。

公开(公告)号：US20120009561A1

公开(公告)日：2012-01-12

申请号：US13237593

申请日：2011-09-20

申请人： William L. WARREN ,  Heather FAHLENKAMP ,  Russell G. HIGBEE ,  Eric M. MISHKIN ,  Guzman SANCHEZ-SCHMITZ ,  Michael D. RIVARD ,  Santosh PAWAR

发明人： William L. WARREN ,  Heather FAHLENKAMP ,  Russell G. HIGBEE ,  Eric M. MISHKIN ,  Guzman SANCHEZ-SCHMITZ ,  Michael D. RIVARD ,  Santosh PAWAR

IPC分类号： C12Q1/70 ,  C12Q1/02

CPC分类号： C12N5/0698 ,  C12N2501/21 ,  C12N2502/091 ,  C12N2502/094 ,  C12N2502/11 ,  C12N2502/1192 ,  C12N2502/1323 ,  C12N2502/28 ,  C12N2502/30 ,  C12N2503/04 ,  C12N2531/00 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2535/10 ,  G01N33/5082

摘要： The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the tissues of the immune system in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates and other materials in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system, coupled with disease models to provide a more complete representation of an immune response.

摘要翻译： 本发明涉及构建综合人造免疫系统的方法，其包括适当的体外细胞和组织构建体或其等同物以模拟哺乳动物免疫系统的组织。 人造免疫系统可用于测试疫苗候选物和其他材料在体外的功效，因此可用于加速疫苗开发和测试与免疫系统的药物和化学相互作用，加上疾病模型，以提供更完整的表达 免疫反应。

公开(公告)号：US20100279277A1

公开(公告)日：2010-11-04

申请号：US12833640

申请日：2010-07-09

申请人： William L. WARREN ,  Heather FAHLENKAMP ,  Russell G. HIGBEE ,  Eric M. MISHKIN ,  Guzman SANCHEZ-SCHMITZ ,  Michael D. RIVARD ,  Santosh PAWAR

发明人： William L. WARREN ,  Heather FAHLENKAMP ,  Russell G. HIGBEE ,  Eric M. MISHKIN ,  Guzman SANCHEZ-SCHMITZ ,  Michael D. RIVARD ,  Santosh PAWAR

IPC分类号： C12Q1/02 ,  C12Q1/70

CPC分类号： C12M21/08 ,  C12M25/14 ,  C12M35/08 ,  C12N5/0651 ,  C12N5/0698 ,  C12N2501/21 ,  C12N2502/091 ,  C12N2502/094 ,  C12N2502/11 ,  C12N2502/1192 ,  C12N2502/1323 ,  C12N2502/28 ,  C12N2502/30 ,  C12N2503/04 ,  C12N2531/00 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2535/10 ,  G01N33/5044 ,  G01N33/5064 ,  G01N33/5082 ,  G01N33/5088 ,  G01N2800/24

摘要： The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the tissues of the immune system in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates and other materials in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system, coupled with disease models to provide a more complete representation of an immune response.

摘要翻译： 本发明涉及构建综合人造免疫系统的方法，其包括适当的体外细胞和组织构建体或其等同物以模拟哺乳动物中免疫系统的组织。 人造免疫系统可用于测试疫苗候选物和其他材料在体外的功效，因此，有助于加速疫苗开发和测试与免疫系统的药物和化学相互作用，加上疾病模型，以提供更完整的表示 免疫反应。