公开(公告)号：US06828150B2

公开(公告)日：2004-12-07

申请号：US10266463

申请日：2002-10-08

申请人： Zeling Cai ,  Jonathan Sprent ,  Anders Brunmark ,  Michael Jackson ,  Per A. Peterson ,  Alain Luxembourg ,  Didier J. Leturcq ,  Ann M. Moriarty

发明人： Zeling Cai ,  Jonathan Sprent ,  Anders Brunmark ,  Michael Jackson ,  Per A. Peterson ,  Alain Luxembourg ,  Didier J. Leturcq ,  Ann M. Moriarty

IPC分类号： C12N500

CPC分类号： C12N5/0601 ,  A61K38/00 ,  A61K2039/5158 ,  C07K14/005 ,  C07K14/70503 ,  C07K14/70539 ,  C12N5/0636 ,  C12N15/85 ,  C12N2501/50 ,  C12N2501/51 ,  C12N2502/50 ,  C12N2502/99 ,  C12N2760/16122 ,  C12N2760/18822 ,  C12N2760/20222 ,  C12N2830/002 ,  C12N2830/75 ,  C12N2830/80 ,  Y10S530/812 ,  Y10S530/827

摘要： The present invention relates to synthetic antigen-presenting matrices, their methods of making and their methods of use. One such matrix is cells that have been transfected to produce MHC antigen-presenting molecules and assisting molecules such as co-stimulatory molecules. The matrices can be used to activate CD8+ T-cells to produce cytokines and become cytotoxic.

摘要翻译： 本发明涉及合成抗原呈递矩阵，其制备方法及其使用方法。 一种这样的基质是已被转染以产生MHC抗原呈递分子并辅助分子如共刺激分子的细胞。 该基质可用于激活CD8 + T细胞以产生细胞因子并变成细胞毒性。

公开(公告)号：US06362001B1

公开(公告)日：2002-03-26

申请号：US09042492

申请日：1998-03-16

申请人： Zeling Cai ,  Jonathan Sprent ,  Anders Brunmark ,  Michael Jackson ,  Per A. Peterson

发明人： Zeling Cai ,  Jonathan Sprent ,  Anders Brunmark ,  Michael Jackson ,  Per A. Peterson

IPC分类号： C12N1563

CPC分类号： C12N5/0601 ,  A61K38/00 ,  A61K2039/5158 ,  C07K14/005 ,  C07K14/70503 ,  C07K14/70539 ,  C12N5/0636 ,  C12N15/85 ,  C12N2501/50 ,  C12N2501/51 ,  C12N2502/50 ,  C12N2502/99 ,  C12N2760/16122 ,  C12N2760/18822 ,  C12N2760/20222 ,  C12N2830/002 ,  C12N2830/75 ,  C12N2830/80 ,  Y10S530/812 ,  Y10S530/827

摘要： Materials and methods of activating T lymphocytes with specificity for particular antigenic peptides are described, as well as the use of activated T lymphocytes in vitro for the treatment of a variety of disease conditions. In particular, a method for producing a synthetic antigen presenting drosophila cell line for activating T lymphocytes to a specific peptide is described.

摘要翻译： 描述了对特定抗原肽具有特异性活化T淋巴细胞的材料和方法，以及活体T淋巴细胞在体外用于治疗各种疾病状况的用途。 特别地，描述了一种用于产生用于将T淋巴细胞活化到特定肽的呈现果蝇细胞系的合成抗原的方法。

公开(公告)号：US20120046645A1

公开(公告)日：2012-02-23

申请号：US13285459

申请日：2011-10-31

申请人： ZELING CAI ,  WEI-XING SHI ,  XUEJUN P. LIU ,  JIEJUN WU

发明人： ZELING CAI ,  WEI-XING SHI ,  XUEJUN P. LIU ,  JIEJUN WU

IPC分类号： A61M37/00 ,  C12N5/0783

CPC分类号： C07K7/08 ,  A61K38/00 ,  A61K39/0011 ,  A61K2039/5158 ,  A61K2039/57 ,  C07K7/06 ,  C07K14/4748 ,  C12N5/0638 ,  C12N2501/2302 ,  C12N2501/2307 ,  C12N2501/51 ,  C12N2501/58 ,  C12N2501/599 ,  C12N2502/50 ,  C12N2502/99

摘要： Multiple myeloma (MM) is a clonal B cell malignancy and remains essentially incurable by conventional anti-tumor therapy. Patients with MM have a median survival of only three years. MM is characterized by proliferation and accumulation of mature plasma cells in the bone marrow (BM) leading to bone destruction, BM failure, anemia, and reduced immune function. The identification of MHC Class I, HLA-A2, associated peptides presented on multiple myeloma cells is an important step in developing immunotherapies for MM. Presented here are methods for creating activated T lymphocytes that are cytotoxic to both peptide loaded T2 target cells and multiple myeloma cell lines.

公开(公告)号：US20120045829A1

公开(公告)日：2012-02-23

申请号：US13285491

申请日：2011-10-31

申请人： ZELING CAI ,  WEI-XING SHI ,  XUEJUN P. LIU ,  JIEJUN WU

发明人： ZELING CAI ,  WEI-XING SHI ,  XUEJUN P. LIU ,  JIEJUN WU

IPC分类号： C12N5/07

CPC分类号： C07K7/08 ,  A61K38/00 ,  A61K39/0011 ,  A61K2039/5158 ,  A61K2039/57 ,  C07K7/06 ,  C07K14/4748 ,  C12N5/0638 ,  C12N2501/2302 ,  C12N2501/2307 ,  C12N2501/51 ,  C12N2501/58 ,  C12N2501/599 ,  C12N2502/50 ,  C12N2502/99

摘要： Multiple myeloma (MM) is a clonal B cell malignancy and remains essentially incurable by conventional anti-tumor therapy. Patients with MM have a median survival of only three years. MM is characterized by proliferation and accumulation of mature plasma cells in the bone marrow (BM) leading to bone destruction, BM failure, anemia, and reduced immune function. The identification of MHC Class I, HLA-A2, associated peptides presented on multiple myeloma cells is an important step in developing immunotherapies for MM. Presented here are methods for creating activated T lymphocytes that are cytotoxic to both peptide loaded T2 target cells and multiple myeloma cell lines.

公开(公告)号：US20110065186A1

公开(公告)日：2011-03-17

申请号：US12899052

申请日：2010-10-06

申请人： Zeling Cai ,  Michael R. Jackson ,  Per A. Peterson ,  Wei-Xing Shi ,  Yan Kong ,  Juli DeGraw

发明人： Zeling Cai ,  Michael R. Jackson ,  Per A. Peterson ,  Wei-Xing Shi ,  Yan Kong ,  Juli DeGraw

IPC分类号： C12N5/10

CPC分类号： A61K39/0008 ,  A61K2035/122 ,  C12N5/0636 ,  C12N2501/23 ,  C12N2501/51 ,  C12N2501/58 ,  C12N2502/50 ,  C12N2502/99

摘要： Cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from IgE molecule can be generated in vitro by stimulating resting naive CD8 T cells with IgE peptides presented by artificial antigen presenting cells. The IgE specific CTLs lyse the target cells loaded with IgE peptides in vitro and inhibit antigen specific IgE response in vivo. In addition, adoptive transfer of the IgE specific CTL to an asthmatic mouse model can inhibit the development of lung inflammation and airway hypersensitivity. IgE specific CTL provides a treatment for allergic asthma and other IgE-mediated allergic diseases. Antigenic peptides identified from non-tumor self-antigens induce specific cytotoxic T lymphocyte (CTL) in vitro. The CTL induced by peptides identified from CD40L can kill activated CD4 T cells. In vitro generated CTL specific for CD40L inhibit CD4-dependent antibody responses of all isotypes in vivo. In contrast, CTL induced by antigenic peptides derived from IgE specifically inhibit IgE responses, and adoptive transfer of CD40L-specific CTL to NOD mice at early age delay the development of diabetes in NOD mice. In vitro generated CTL specific for non-tumor self-antigens expressed on activated CD4 T cells regulate immune responses in vivo.

公开(公告)号：US20110027301A1

公开(公告)日：2011-02-03

申请号：US12887032

申请日：2010-09-21

申请人： Zeling Cai ,  Michael R. Jackson ,  Per A. Peterson ,  Wei-Xing Shi ,  Yan Kong ,  Juli DeGraw

发明人： Zeling Cai ,  Michael R. Jackson ,  Per A. Peterson ,  Wei-Xing Shi ,  Yan Kong ,  Juli DeGraw

IPC分类号： A61K39/00 ,  A61P37/08 ,  A61P11/06 ,  C12N5/02

CPC分类号： A61K39/0008 ,  A61K2035/122 ,  C12N5/0636 ,  C12N2501/23 ,  C12N2501/51 ,  C12N2501/58 ,  C12N2502/50 ,  C12N2502/99

摘要： Cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from IgE molecule can be generated in vitro by stimulating resting naive CD8 T cells with IgE peptides presented by artificial antigen presenting cells. The IgE specific CTLs lyse the target cells loaded with IgE peptides in vitro and inhibit antigen specific IgE response in vivo. In addition, adoptive transfer of the IgE specific CTL to an asthmatic mouse model can inhibit the development of lung inflammation and airway hypersensitivity. IgE specific CTL provides a treatment for allergic asthma and other IgE-mediated allergic diseases. Antigenic peptides identified from non-tumor self-antigens induce specific cytotoxic T lymphocyte (CTL) in vitro. The CTL induced by peptides identified from CD40L can kill activated CD4 T cells. In vitro generated CTL specific for CD40L inhibit CD4-dependent antibody responses of all isotypes in vivo. In contrast, CTL induced by antigenic peptides derived from IgE specifically inhibit IgE responses, and adoptive transfer of CD40L-specific CTL to NOD mice at early age delay the development of diabetes in NOD mice. In vitro generated CTL specific for non-tumor self-antigens expressed on activated CD4 T cells regulate immune responses in vivo.

公开(公告)号：US20110021747A1

公开(公告)日：2011-01-27

申请号：US12892060

申请日：2010-09-28

申请人： Zeling Cai ,  Michael R. Jackson ,  Per A. Peterson ,  Wei-Xing Shi ,  Yan Kong ,  Juli DeGraw

发明人： Zeling Cai ,  Michael R. Jackson ,  Per A. Peterson ,  Wei-Xing Shi ,  Yan Kong ,  Juli DeGraw

IPC分类号： C07K7/06

CPC分类号： A61K39/0008 ,  A61K2035/122 ,  C12N5/0636 ,  C12N2501/23 ,  C12N2501/51 ,  C12N2501/58 ,  C12N2502/50 ,  C12N2502/99

摘要： Cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from IgE molecule can be generated in vitro by stimulating resting naive CD8 T cells with IgE peptides presented by artificial antigen presenting cells. The IgE specific CTLs lyse the target cells loaded with IgE peptides in vitro and inhibit antigen specific IgE response in vivo. In addition, adoptive transfer of the IgE specific CTL to an asthmatic mouse model can inhibit the development of lung inflammation and airway hypersensitivity. IgE specific CTL provides a treatment for allergic asthma and other IgE-mediated allergic diseases. Antigenic peptides identified from non-tumor self-antigens induce specific cytotoxic T lymphocyte (CTL) in vitro. The CTL induced by peptides identified from CD40L can kill activated CD4 T cells. In vitro generated CTL specific for CD40L inhibit CD4-dependent antibody responses of all isotypes in vivo. In contrast, CTL induced by antigenic peptides derived from IgE specifically inhibit IgE responses, and adoptive transfer of CD40L-specific CTL to NOD mice at early age delay the development of diabetes in NOD mice. In vitro generated CTL specific for non-tumor self-antigens expressed on activated CD4 T cells regulate immune responses in vivo.

公开(公告)号：US20110020309A1

公开(公告)日：2011-01-27

申请号：US12887052

申请日：2010-09-21

申请人： Zeling Cai ,  Michael R. Jackson ,  Per A. Peterson ,  Wei-Xing Shi ,  Yan Kong ,  Juli DeGraw

发明人： Zeling Cai ,  Michael R. Jackson ,  Per A. Peterson ,  Wei-Xing Shi ,  Yan Kong ,  Juli DeGraw

IPC分类号： A61K35/12 ,  C12N5/0783 ,  A61P37/02 ,  A61P3/10 ,  A61P29/00 ,  A61P17/06 ,  A61P25/00

CPC分类号： A61K39/0008 ,  A61K2035/122 ,  C12N5/0636 ,  C12N2501/23 ,  C12N2501/51 ,  C12N2501/58 ,  C12N2502/50 ,  C12N2502/99

摘要： Cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from IgE molecule can be generated in vitro by stimulating resting naive CD8 T cells with IgE peptides presented by artificial antigen presenting cells. The IgE specific CTLs lyse the target cells loaded with IgE peptides in vitro and inhibit antigen specific IgE response in vivo. In addition, adoptive transfer of the IgE specific CTL to an asthmatic mouse model can inhibit the development of lung inflammation and airway hypersensitivity. IgE specific CTL provides a treatment for allergic asthma and other IgE-mediated allergic diseases. Antigenic peptides identified from non-tumor self-antigens induce specific cytotoxic T lymphocyte (CTL) in vitro. The CTL induced by peptides identified from CD40L can kill activated CD4 T cells. In vitro generated CTL specific for CD40L inhibit CD4-dependent antibody responses of all isotypes in vivo. In contrast, CTL induced by antigenic peptides derived from IgE specifically inhibit IgE responses, and adoptive transfer of CD40L-specific CTL to NOD mice at early age delay the development of diabetes in NOD mice. In vitro generated CTL specific for non-tumor self-antigens expressed on activated CD4 T cells regulate immune responses in vivo.

摘要翻译： 可以通过用人造抗原呈递细胞呈递的IgE肽刺激静息幼稚CD8T细胞在体外产生来自IgE分子的抗原肽特异性的细胞毒性T淋巴细胞（CTL）。 IgE特异性CTL在体外裂解装载有IgE肽的靶细胞，并在体内抑制抗原特异性IgE反应。 此外，将IgE特异性CTL过继转移至哮喘小鼠模型可以抑制肺部炎症和气道超敏反应的发展。 IgE特异性CTL提供过敏性哮喘和其他IgE介导的过敏性疾病的治疗。 从非肿瘤自身抗原鉴定的抗原肽在体外诱导特异性细胞毒性T淋巴细胞（CTL）。 由CD40L鉴定的肽诱导的CTL可以杀死活化的CD4T细胞。 体外产生的CD40L特异性CTL可抑制体内所有同种型的CD4依赖性抗体反应。 相比之下，来自IgE的抗原肽诱导的CTL特异性抑制IgE应答，CD40L特异性CTL过早转移到NOD小鼠早期延迟NOD小鼠的糖尿病发展。 在活化的CD4T细胞上表达的非肿瘤自身抗原的体外产生的CTL调节体内的免疫应答。

公开(公告)号：US07842501B2

公开(公告)日：2010-11-30

申请号：US11935486

申请日：2007-11-06

申请人： Zeling Cai ,  Michael R. Jackson ,  Per A. Peterson ,  Wei-Xing Shi ,  Yan Kong ,  Juli DeGraw

发明人： Zeling Cai ,  Michael R. Jackson ,  Per A. Peterson ,  Wei-Xing Shi ,  Yan Kong ,  Juli DeGraw

IPC分类号： C12N5/08

CPC分类号： A61K39/0008 ,  A61K2035/122 ,  C12N5/0636 ,  C12N2501/23 ,  C12N2501/51 ,  C12N2501/58 ,  C12N2502/50 ,  C12N2502/99

摘要： Cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from IgE molecule can be generated in vitro by stimulating resting naive CD8 T cells with IgE peptides presented by artificial antigen presenting cells. The IgE specific CTLs lyse the target cells loaded with IgE peptides in vitro and inhibit antigen specific IgE response in vivo. In addition, adoptive transfer of the IgE specific CTL to an asthmatic mouse model can inhibit the development of lung inflammation and airway hypersensitivity. IgE specific CTL provides a treatment for allergic asthma and other IgE-mediated allergic diseases. Antigenic peptides identified from non-tumor self-antigens induce specific cytotoxic T lymphocyte (CTL) in vitro. The CTL induced by peptides identified from CD40L can kill activated CD4 T cells. In vitro generated CTL specific for CD40L inhibit CD4-dependent antibody responses of all isotypes in vivo. In contrast, CTL induced by antigenic peptides derived from IgE specifically inhibit IgE responses, and adoptive transfer of CD40L-specific CTL to NOD mice at early age delay the development of diabetes in NOD mice. In vitro generated CTL specific for non-tumor self-antigens expressed on activated CD4 T cells regulate immune responses in vivo.

摘要翻译： 可以通过用人造抗原呈递细胞呈递的IgE肽刺激静息幼稚CD8T细胞在体外产生来自IgE分子的抗原肽特异性的细胞毒性T淋巴细胞（CTL）。 IgE特异性CTL在体外裂解装载有IgE肽的靶细胞，并在体内抑制抗原特异性IgE反应。 此外，将IgE特异性CTL过继转移至哮喘小鼠模型可以抑制肺部炎症和气道超敏反应的发展。 IgE特异性CTL提供过敏性哮喘和其他IgE介导的过敏性疾病的治疗。 从非肿瘤自身抗原鉴定的抗原肽在体外诱导特异性细胞毒性T淋巴细胞（CTL）。 由CD40L鉴定的肽诱导的CTL可以杀死活化的CD4T细胞。 体外产生的CD40L特异性CTL可抑制体内所有同种型的CD4依赖性抗体反应。 相比之下，来自IgE的抗原肽诱导的CTL特异性抑制IgE应答，CD40L特异性CTL过早转移到NOD小鼠早期延迟NOD小鼠的糖尿病发展。 在活化的CD4T细胞上表达的非肿瘤自身抗原的体外产生的CTL调节体内的免疫应答。

公开(公告)号：US20090075372A1

公开(公告)日：2009-03-19

申请号：US11994337

申请日：2006-07-03

申请人： Herve Groux ,  Francoise Cottrez

发明人： Herve Groux ,  Francoise Cottrez

IPC分类号： C12N5/08 ,  C12N5/06

CPC分类号： A61K39/0008 ,  A61K2035/122 ,  A61K2039/5158 ,  C12N5/0636 ,  C12N2500/90 ,  C12N2500/95 ,  C12N2501/23 ,  C12N2501/51 ,  C12N2501/515 ,  C12N2501/53 ,  C12N2502/50 ,  C12N2502/99

摘要： An in vitro method for the obtention of a food- or auto-antigen specific Tr1 cell population from a leukocyte or a PBMC population, includes stimulating the PBMC or leukocyte population with the food- or auto-antigen, and recovering the food- or auto-antigen specific Tr1 cell population from the stimulated cell population. Preferably, the PBMC or leukocyte population is re-stimulated at least once with the same antigen after step (1), in the presence of IL-2 and at least one interleukin selected from the group consisting of IL-4 and IL-13. The in vitro method may further include a third step of expanding the recovered antigen-specific Tr1 cell population, advantageously by contacting them with feeder cells capable of expressing factors necessary for the expansion. Preferably, the feeder cells are recombinant insect feeder cells.

摘要翻译： 用于从白细胞或PBMC群体获得食物或自身抗原特异性Tr1细胞群体的体外方法包括用食物或自身抗原刺激PBMC或白细胞群体，并回收食物或自动抗体 来自刺激细胞群的抗原特异性Tr1细胞群体。 优选地，在IL-2和至少一种选自IL-4和IL-13的白介素的存在下，在步骤（1）之后，使用相同的抗原将PBMC或白细胞群重新刺激至少一次。 体外方法还可以包括扩增回收的抗原特异性Tr1细胞群体的第三步骤，有利地通过使其与能够表达扩增所必需的因子的饲养细胞接触。 饲养细胞优选是重组昆虫饲养细胞。