公开(公告)号：US20060078540A1

公开(公告)日：2006-04-13

申请号：US10508350

申请日：2003-03-18

申请人： William Warren ,  Nir Hacohen ,  Lan Chen ,  Darell Irvine ,  Anatoly Kachurin ,  Russell Higbee ,  Qian Huang

发明人： William Warren ,  Nir Hacohen ,  Lan Chen ,  Darell Irvine ,  Anatoly Kachurin ,  Russell Higbee ,  Qian Huang

IPC分类号： C12N5/08 ,  A61K48/00 ,  A61K35/14

CPC分类号： C12N5/0697 ,  A61K2039/5154 ,  C12N5/0639 ,  C12N2502/11

摘要： The present invention features dendritic cell nodes that can be used to vaccinate subjects against pathogens and to modulate a subject's immune system to treat or prevent various diseases and conditions.

摘要翻译： 本发明具有树突细胞节点，其可用于针对病原体接种受试者并调节受试者的免疫系统以治疗或预防各种疾病和病症。

公开(公告)号：US08298823B2

公开(公告)日：2012-10-30

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： C12N5/16 ,  C12N5/02

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：US08247226B2

公开(公告)日：2012-08-21

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 ,  Conan Li ,  Anatoly M. Kachurin ,  Russell Higbee ,  Heather Fahlenkamp ,  Eric Mishkin ,  William L. Warren

发明人： Selva Sukumar ,  Mohey Eldin M. El Shikh ,  John G. Tew ,  Guzman Sanchez-Schmitz ,  Donald Drake, III ,  Luis Mosquera ,  Conan Li ,  Anatoly M. Kachurin ,  Russell Higbee ,  Heather Fahlenkamp ,  Eric Mishkin ,  William L. Warren

IPC分类号： C12N5/00 ,  C12N5/02

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：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：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：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：US08003385B2

公开(公告)日：2011-08-23

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 ,  Conan Li ,  Anatoly M. Kachurin ,  Russell Higbee ,  Heather Fahlenkamp ,  Eric Mishkin ,  William L. Warren

发明人： Selva Sukumar ,  Mohey Eldin M. El Shikh ,  John G. Tew ,  Guzman Sanchez-Schmitz ,  Donald Drake, III ,  Luis Mosquera ,  Conan Li ,  Anatoly M. Kachurin ,  Russell Higbee ,  Heather Fahlenkamp ,  Eric Mishkin ,  William L. Warren

IPC分类号： C12N5/06 ,  C12N5/02

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.

公开(公告)号：US07785883B2

公开(公告)日：2010-08-31

申请号：US11375033

申请日：2006-03-15

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： C12N5/08

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：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。