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    A CELL THERAPY METHOD FOR THE TREATMENT OF TUMORS
    7.
    发明申请
    A CELL THERAPY METHOD FOR THE TREATMENT OF TUMORS 有权
    用于治疗肿瘤的细胞治疗方法

    公开(公告)号：US20090004142A1

    公开(公告)日：2009-01-01

    申请号：US11782264

    申请日：2007-07-24

    申请人： Didier J. Leturcq ,  Ann M. Moriarty ,  Michael R. Jackson ,  Per A. Peterson ,  Jon M. Richards

    发明人： Didier J. Leturcq ,  Ann M. Moriarty ,  Michael R. Jackson ,  Per A. Peterson ,  Jon M. Richards

    IPC分类号： A61K38/21 ,  A61K35/12 ,  A61P35/00

    CPC分类号： C12N5/0636 ,  A61K38/2013 ,  A61K38/212 ,  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 ,  A61K2300/00

    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（AAPCs;黑腹果蝇）用人类HLA I类和定义的辅助分子转染，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。

    Cell therapy method for the treatment of tumors
    9.
    发明授权
    Cell therapy method for the treatment of tumors 有权
    用于治疗肿瘤的细胞治疗方法

    公开(公告)号：US09222071B2

    公开(公告)日：2015-12-29

    申请号：US12014863

    申请日：2008-01-16

    申请人： Ann Moriarty ,  Didier J. Leturcq ,  Juli Degraw ,  Michael R. Jackson ,  Per A. Peterson ,  Marja Heiskala

    发明人： Ann Moriarty ,  Didier J. Leturcq ,  Juli Degraw ,  Michael R. Jackson ,  Per A. Peterson ,  Marja Heiskala

    IPC分类号： C12N5/10 ,  C12N5/00 ,  C12N5/0783 ,  A61K48/00 ,  A61K39/00 ,  A61K41/00 ,  C12N5/07 ,  A61K35/12

    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。

    Ex-vivo priming for generating cytotoxic T lymphocytes specific for non-tumor antigens to treat autoimmune and allergic disease
    10.
    发明授权
    Ex-vivo priming for generating cytotoxic T lymphocytes specific for non-tumor antigens to treat autoimmune and allergic disease 有权
    用于产生特异于非肿瘤抗原的细胞毒性T淋巴细胞用于治疗自身免疫性和过敏性疾病的体外引发

    公开(公告)号：US08084256B2

    公开(公告)日：2011-12-27

    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： C12N5/00 ,  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.

    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。