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    CELL THERAPY METHOD FOR THE TREATMENT OF TUMORS
    36.
    发明申请
    CELL THERAPY METHOD FOR THE TREATMENT OF TUMORS 有权
    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。

    Purification of antigen-specific T cells
    37.
    发明授权
    Purification of antigen-specific T cells 有权
    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。