公开(公告)号：US08697371B2

公开(公告)日：2014-04-15

申请号：US13288401

申请日：2011-11-03

申请人： William L. Warren ,  Donald Drake, III ,  Janice Moser ,  Inderpal Singh ,  Haifeng Song ,  Eric Mishkin ,  John G. Tew

发明人： William L. Warren ,  Donald Drake, III ,  Janice Moser ,  Inderpal Singh ,  Haifeng Song ,  Eric Mishkin ,  John G. Tew

IPC分类号： G01N33/567 ,  C12N5/00 ,  C12N5/08

CPC分类号： G01N33/5052 ,  C12N5/0635 ,  C12N5/0636 ,  C12N5/0639 ,  C12N5/0697 ,  C12N2500/90 ,  C12N2501/21 ,  C12N2502/1107 ,  C12N2502/1114 ,  C12N2502/1121 ,  C12N2502/28 ,  C12N2503/04 ,  C12N2510/04 ,  C12N2531/00 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2535/10 ,  G01N33/505 ,  G01N33/5088

摘要： The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising T cells, B cells and antigen-primed dendritic 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。 人造免疫系统包括包含T细胞，B细胞和抗原引发的树突状细胞的细胞培养物。 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：US08962319B2

公开(公告)日：2015-02-24

申请号：US13289024

申请日：2011-11-04

申请人： William L. Warren ,  Donald Drake, III ,  Janice Moser ,  Inderpal Singh ,  Haifeng Song ,  Eric Mishkin ,  John G. Tew

发明人： William L. Warren ,  Donald Drake, III ,  Janice Moser ,  Inderpal Singh ,  Haifeng Song ,  Eric Mishkin ,  John G. Tew

IPC分类号： C12N5/00 ,  C12N5/02 ,  G01N33/50 ,  C12N5/0781 ,  C12N5/0783 ,  C12N5/0784 ,  C12N5/071

CPC分类号： G01N33/5052 ,  C12N5/0635 ,  C12N5/0636 ,  C12N5/0639 ,  C12N5/0697 ,  C12N2500/90 ,  C12N2501/21 ,  C12N2502/1107 ,  C12N2502/1114 ,  C12N2502/1121 ,  C12N2502/28 ,  C12N2503/04 ,  C12N2510/04 ,  C12N2531/00 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2535/10 ,  G01N33/505 ,  G01N33/5088

摘要： The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising T cells, B cells and antigen-primed dendritic 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。 人造免疫系统包括包含T细胞，B细胞和抗原引发的树突状细胞的细胞培养物。 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：US08071373B2

公开(公告)日：2011-12-06

申请号：US11453046

申请日：2006-06-15

申请人： William L. Warren ,  Donald Drake, III ,  Janice Moser ,  Inderpal Singh ,  Haifeng Song ,  Eric Mishkin ,  John G. Tew

发明人： William L. Warren ,  Donald Drake, III ,  Janice Moser ,  Inderpal Singh ,  Haifeng Song ,  Eric Mishkin ,  John G. Tew

IPC分类号： C12N5/00 ,  C12N5/08

CPC分类号： G01N33/5052 ,  C12N5/0635 ,  C12N5/0636 ,  C12N5/0639 ,  C12N5/0697 ,  C12N2500/90 ,  C12N2501/21 ,  C12N2502/1107 ,  C12N2502/1114 ,  C12N2502/1121 ,  C12N2502/28 ,  C12N2503/04 ,  C12N2510/04 ,  C12N2531/00 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2535/10 ,  G01N33/505 ,  G01N33/5088

摘要： The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising T cells, B cells and antigen-primed dendritic 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。 人造免疫系统包括包含T细胞，B细胞和抗原引发的树突状细胞的细胞培养物。 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：US07709257B2

公开(公告)日：2010-05-04

申请号：US11819335

申请日：2007-06-27

申请人： John G. Tew ,  Mohey Eldin M. El Shikh ,  Inderpal Singh ,  Eric Mishkin ,  Donald Drake, III ,  Haifeng Song ,  William L Warren

发明人： John G. Tew ,  Mohey Eldin M. El Shikh ,  Inderpal Singh ,  Eric Mishkin ,  Donald Drake, III ,  Haifeng Song ,  William L Warren

IPC分类号： C12N5/00 ,  C12N5/02 ,  C12N5/16

CPC分类号： A01K67/0271 ,  A01K2267/0337 ,  A61K49/0008

摘要： The present invention is directed to methods for constructing and using in vivo and in vitro models of aspects of human immunity and, in particular, construction of a human immune system model for the testing of, for example, vaccines, adjuvants, immunotherapy candidates, cosmetics, drugs, biologics and other chemicals. The present invention comprises both in vivo and in vitro models of aspects of human immunity that are useful for assessing the interaction of substances with the immune system, and thus can be used to accelerate and improve the accuracy and predictability of, for example, vaccine, drug, biologic, immunotherapy, cosmetic and chemical development. The invention is also useful for the generation of human monoclonal and polyclonal antibodies.

摘要翻译： 本发明涉及用于构建和使用人体免疫方面的体内和体外模型的方法，特别是建立用于例如疫苗，佐剂，免疫治疗候选物，化妆品的测试的人类免疫系统模型 ，药物，生物制剂等化学品。 本发明包括可用于评估物质与免疫系统的相互作用的人体免疫方面的体内和体外模型，因此可用于加速和提高例如疫苗的准确性和可预测性， 药物，生物，免疫治疗，化妆品和化学发展。 本发明也可用于产生人单克隆抗体和多克隆抗体。

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：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：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

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：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

IPC分类号： C12N5/08 ,  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：US20090104221A1

公开(公告)日：2009-04-23

申请号：US12167689

申请日：2008-07-03

申请人： Mohey Eldin Moustafa El Shikh ,  Rania El Sayed ,  Andras K. Szakal ,  John G. Tew ,  Donald R. Drake, III ,  Vaughan Wittman ,  Jennifer Eatrides ,  William L. Warren

发明人： Mohey Eldin Moustafa El Shikh ,  Rania El Sayed ,  Andras K. Szakal ,  John G. Tew ,  Donald R. Drake, III ,  Vaughan Wittman ,  Jennifer Eatrides ,  William L. Warren

IPC分类号： A61K39/00 ,  C12Q1/02 ,  C12P21/00

CPC分类号： G01N33/5052 ,  A61K39/00 ,  A61K2039/545 ,  A61K2039/55505 ,  A61K2039/6012 ,  A61K2039/6056 ,  C07K16/4283 ,  C12N5/0639 ,  C12N2503/02 ,  G01N33/5044 ,  G01N33/505 ,  G01N33/5082

摘要： The present invention comprises the use of follicular dendritic cells (FDCs) or FDC-like cells to generate FDC-dependent, but T cell-independent, B cell responses to T cell-dependent antigens, with antigen-specific and polyclonal antibody production in ˜48 h. In another embodiment, a germinal center (GC) lymphoid tissue equivalent (LTE) was used to generate antigen-specific IgM, followed by switching to IgG. The GC LTE model can be used in vaccine assessment. Dual forms of immunogen were used in the GC LTE and in vivo. Dual immunogens resulted in rapid, specific IgM responses and enhanced IgG responses. This vaccine design approach can be used, for example, to provide rapid IgM protection (˜24-48 h) and high-affinity IgG more quickly in people moving to areas with endemic disease, or in people with T cell insufficiencies, who can be immunized to rapidly generate protective IgM.

摘要翻译： 本发明包括使用滤泡树突状细胞（FDC）或FDC样细胞来产生FDC依赖但与T细胞无关的B细胞对T细胞依赖性抗原的应答，其中抗原特异性和多克隆抗体产生在〜 48小时。 在另一个实施方案中，使用生发中心（GC）淋巴组织等同物（LTE）产生抗原特异性IgM，随后切换至IgG。 GC LTE模型可用于疫苗评估。 免疫原的双重形式用于GC LTE和体内。 双重免疫原导致快速，特异性IgM反应和增强的IgG反应。 例如，这种疫苗设计方法可以用于在移动到地方性疾病地区的人群中或在具有T细胞功能不足的人群中提供快速的IgM保护（〜24-48小时）和高亲和力IgG 免疫以快速产生保护性IgM。