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41. 发明授权

US07811816B2 Isolated CD8 +T lymphocytes specifically cytotoxic for a disease causing target cell 有权
标题翻译：孤立的CD8 + T淋巴细胞特异性细胞毒性致病目标细胞
公开(公告)号：US07811816B2
公开(公告)日：2010-10-12
申请号：US10144188
申请日：2002-05-13
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。

42. 发明申请

US20090305418A1 CELL THERAPY METHOD FOR THE TREATMENT OF TUMORS 有权
标题翻译：细胞治疗方法治疗肿瘤
公开(公告)号：US20090305418A1
公开(公告)日：2009-12-10
申请号：US12014863
申请日：2008-01-16
申请人： Ann Moriarty , Didier J. Leturqc , Juli Degraw , Michael R. Jackson , Per A. Peterson , Marja Heiskala
发明人： Ann Moriarty , Didier J. Leturqc , Juli Degraw , Michael R. Jackson , Per A. Peterson , Marja Heiskala
IPC分类号： C12N15/63 , C12N5/10
CPC分类号： C12N5/0636 , A61K39/0011 , A61K41/00 , A61K48/00 , A61K2035/124 , A61K2039/5154 , A61K2039/5156 , A61K2039/5158 , A61K2039/55527 , A61K2039/55533 , A61K2039/55538 , C12N5/0601 , C12N2501/23 , C12N2501/515 , C12N2502/99 , C12N2510/00
摘要： T cell responses are often diminished in humans with a compromised immune system. We have developed a method to isolate, stimulate and expand naïve cytotoxic T lymphocyte precursors (CTLp) to antigen-specific effectors, capable of lysing tumor cells in vivo. This ex vivo protocol produces fully functional effectors. Artificial antigen presenting cells (AAPCs; Drosophila melanogaster) transfected with human HLA class I and defined accessory molecules, are used to stimulate CD8+ T cells from both normal donors and cancer patients. The class I molecules expressed to a high density on the surface of the Drosophila cells are empty, allowing for efficient loading of multiple peptides that results in the generation of polyclonal responses recognizing tumor cells endogenously expressing the specific peptides. The responses generated are robust, antigen-specific and reproducible if the peptide epitope is a defined immunogen. This artificial antigen expression system can be adapted to treat most cancers in a significant majority of the population.
摘要翻译：免疫系统受损的人类T细胞反应往往减少。我们已经开发出一种方法来分离，刺激并扩增能够在体内裂解肿瘤细胞的抗原特异性效应子的初始细胞毒性T淋巴细胞前体（CTLp）。这种离体协议产生完全功能的效应器。人类抗原呈递细胞（AAPC;黑腹果蝇）转染人类HLA I类和定义的辅助分子，用于刺激来自正常供体和癌症患者的CD8 + T细胞。在果蝇细胞表面上以高密度表达的I类分子是空的，允许有效负载多个肽，导致产生识别内源表达特定肽的肿瘤细胞的多克隆应答。如果肽表位是定义的免疫原，所产生的响应是鲁棒的，抗原特异性的和可重复的。这种人造抗原表达系统可以适应于治疗绝大多数人群中的大多数癌症。

43. 发明授权

US07125964B2 Purification of antigen-specific T cells 有权
标题翻译：抗原特异性T细胞的纯化
公开(公告)号：US07125964B2
公开(公告)日：2006-10-24
申请号：US10785472
申请日：2004-02-23
申请人： Alain T. Luxembourg , Michael R. Jackson , Per A. Peterson
发明人： Alain T. Luxembourg , Michael R. Jackson , Per A. Peterson
IPC分类号： C07K14/74
CPC分类号： A61K39/39 , A61K2039/5158 , C07K16/2818 , C12N5/0636 , C12N2501/51 , G01N33/5094 , G01N33/54326 , G01N33/56977
摘要： A new method to capture, purify and expand antigen-specific T lymphocytes has been developed using magnetic beads coated with recombinant MHC class I molecules. This method was optimized using homogenous populations of naive T cells purified from mice transgenic for the 2C T cell receptor (TCR). These T cells were captured on beads coated with MHC class I molecules and the relevant antigenic peptides. MHC and peptide specificity was confirmed by the usage of irrelevant MHC peptide combinations. An enrichment of 800 to 1600 fold was measured, using 2C T cells mixed with irrelevant T cells, starting from a 2C T cell frequency of 1/3000. The same approach was used to purify antigen-specific CD8+ T cells from total CD8+ T cells from naive mice. The recovered cells could be expanded and specifically kill target cells in vitro; they had a significant effect in vivo as well. We expect this procedure to be suitable to purify and expand in vitro tumor- and virus-specific killer T cells for use in cell therapy.
摘要翻译：已经使用涂覆有重组MHC I类分子的磁珠来开发捕获，纯化和扩增抗原特异性T淋巴细胞的新方法。使用从2CT细胞受体（TCR）转基因小鼠纯化的纯化T细胞的均质群体优化该方法。将这些T细胞捕获在涂有MHC I类分子和相关抗原肽的珠上。通过使用不相关的MHC肽组合证实MHC和肽特异性。使用与不相关的T细胞混合的2CT细胞，从2CT细胞频率1/3000开始，测量浓度为800至1600倍。使用相同的方法从幼稚小鼠的总CD8 + T细胞中纯化抗原特异性CD8 + T细胞。回收的细胞可以扩增并特异性地在体外杀死靶细胞; 它们在体内也具有显着的作用。我们期望这个程序适合于净化和扩大体外肿瘤和病毒特异性杀伤T细胞用于细胞治疗。

44. 发明授权

US06225525B1 ATP-binding cassette transporter (ABC1) modified transgenic mice 有权
标题翻译： ATP结合盒转运蛋白（ABC1）修饰的转基因小鼠
公开(公告)号：US06225525B1
公开(公告)日：2001-05-01
申请号：US09417619
申请日：1999-10-13
申请人： Wai-Ping Leung , Trudy Christiansen-Weber , Joseph R. Voland , Per A. Peterson
发明人： Wai-Ping Leung , Trudy Christiansen-Weber , Joseph R. Voland , Per A. Peterson
IPC分类号： A01K67027
CPC分类号： C07K14/705 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/0306 , C12N15/8509
摘要： A transgenic mouse with alterations in an abc1 gene is prepared by introduction of an altered abc1 gene into a host animal. The resulting transgenic mice do not produce functional ABC1 protein molecules. Cells and cell lines derived from these animals also contain the altered abc1 gene.
摘要翻译：通过将改变的abc1基因导入宿主动物来制备具有abc1基因改变的转基因小鼠。所得到的转基因小鼠不产生功能性ABC1蛋白质分子。衍生自这些动物的细胞和细胞系也含有改变的abc1基因。

45. 发明授权

US5314813A Drosophila cell lines expressing genes encoding MHC class I antigens and B2-microglobulin and capable of assembling empty complexes and methods of making said cell lines 失效
标题翻译：表达编码MHC I类抗原和B2微球蛋白并能组装空复合物的基因的果蝇细胞系和制备所述细胞系的方法
公开(公告)号：US5314813A
公开(公告)日：1994-05-24
申请号：US841662
申请日：1992-02-19
申请人： Per A. Peterson , Michael Jackson , Pierre Langlade-Demoyen
发明人： Per A. Peterson , Michael Jackson , Pierre Langlade-Demoyen
IPC分类号： C12N15/09 , A61K35/14 , A61K35/17 , A61K35/64 , A61K39/00 , A61K47/48 , A61P37/00 , A61P37/02 , C07K14/74 , C12N1/19 , C12N5/00 , C12N5/07 , C12N5/10 , C12N15/85 , C12R1/91 , C12N15/00
CPC分类号： C12N5/0601 , A61K35/17 , A61K47/48776 , C07K14/70539 , C12N15/85 , A61K2039/5154 , A61K2039/5156 , C12N2510/00 , C12N2830/002 , C12N2830/75
摘要： The present invention relates to a rational, elegant means of producing, loading and using Class I molecules to specifically activate CD8 cells in vitro, and their therapeutic applications in the treatment of a variety of conditions, including cancer, tumors or neoplasias, as well as viral, retroviral, autoimmune, and autoimmune-type diseases. The present invention also relates to vectors, cell lines, recombinant DNA molecules encoding human .beta.2 microglobulin or Class I MHC molecules in soluble and insoluble form, and methods of producing same.
摘要翻译：本发明涉及生产，加载和使用I类分子以体外特异性激活CD8细胞的合理，优雅的手段，以及它们在治疗各种病症（包括癌症，肿瘤或肿瘤）中的治疗应用，以及病毒，逆转录病毒，自身免疫和自身免疫性疾病。本发明还涉及可溶性和不溶形式的编码人β2微球蛋白或I类MHC分子的载体，细胞系，重组DNA分子及其生产方法。

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