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公开(公告)号：US08669105B2
公开(公告)日：2014-03-11
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 , 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
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。
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公开(公告)号：US08119403B2
公开(公告)日：2012-02-21
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
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。
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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。
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公开(公告)号：US08003387B2
公开(公告)日：2011-08-23
申请号：US11642938
申请日：2006-12-21
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
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。
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公开(公告)号：US07709256B2
公开(公告)日：2010-05-04
申请号：US11453003
申请日：2006-06-15
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： C12N5/06
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。
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6.发明申请Controlling dendritic cell maturation state in the lymphoid tissue equivalent of an artificial immune system 有权控制人造免疫系统的淋巴组织等效的树突状细胞成熟状态公开(公告)号：US20070015136A1
公开(公告)日：2007-01-18
申请号：US11471514
申请日：2006-06-21
申请人： Guzman Sanchez-Schmitz , Russell Higbee , Heather Fahlenkamp , Darrell Irvine , William Warren , Donald Drake
发明人： Guzman Sanchez-Schmitz , Russell Higbee , Heather Fahlenkamp , Darrell Irvine , William Warren , Donald Drake
CPC分类号： C12N5/0639 , C12N5/0651 , C12N5/0697 , C12N2501/21 , C12N2502/1107 , C12N2502/1114 , C12N2502/1121 , C12N2502/1192 , C12N2502/28 , C12N2503/04 , C12N2533/50 , C12N2533/54 , C12N2535/10 , G01N33/5047
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。
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公开(公告)号：US20060275270A1
公开(公告)日：2006-12-07
申请号：US11375128
申请日：2006-03-15
申请人： William Warren , Guzman Sanchez-Schmitz , Russell Higbee , Heather Fahlenkamp , Donald Drake , John Tew
发明人： William Warren , Guzman Sanchez-Schmitz , Russell Higbee , Heather Fahlenkamp , Donald Drake , John Tew
CPC分类号： C12N5/0697 , C12N2501/21 , C12N2502/094 , C12N2502/11 , C12N2502/1107 , C12N2502/1114 , C12N2502/1121 , C12N2502/1192 , C12N2502/1323 , C12N2502/28 , C12N2503/04 , C12N2533/50 , C12N2533/54 , C12N2533/92 , C12N2535/10 , G01N33/5044 , G01N33/564
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 pathogens and 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病原体和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。
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公开(公告)号：US08288159B2
公开(公告)日：2012-10-16
申请号：US12725698
申请日：2010-03-17
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 Harcohen , 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 Harcohen , Bruce Torbett
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。
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公开(公告)号：US08030070B2
公开(公告)日：2011-10-04
申请号：US11471514
申请日：2006-06-21
申请人： Guzman Sanchez-Schmitz , Russell Higbee , Heather Fahlenkamp , Darrell J. Irvine , William L. Warren , Donald Drake, III
发明人： Guzman Sanchez-Schmitz , Russell Higbee , Heather Fahlenkamp , Darrell J. Irvine , William L. Warren , Donald Drake, III
IPC分类号： C12N5/0781 , C12N5/0783 , C12N5/0784
CPC分类号： C12N5/0639 , C12N5/0651 , C12N5/0697 , C12N2501/21 , C12N2502/1107 , C12N2502/1114 , C12N2502/1121 , C12N2502/1192 , C12N2502/28 , C12N2503/04 , C12N2533/50 , C12N2533/54 , C12N2535/10 , G01N33/5047
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。
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公开(公告)号：US20110171689A1
公开(公告)日：2011-07-14
申请号：US12725698
申请日：2010-03-17
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： C12P21/00
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。
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