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公开(公告)号：US20090004142A1
公开(公告)日：2009-01-01
申请号：US11782264
申请日：2007-07-24
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。
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公开(公告)号：US09222070B2
公开(公告)日：2015-12-29
申请号：US11782264
申请日：2007-07-24
IPC分类号： C12N5/071 , C12N5/0783 , A61K48/00 , A61K38/20 , A61K38/21 , A61K39/00 , A61K41/00 , C12N5/07 , A61K35/12
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.
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3.发明申请公开(公告)号：US20090324539A1
公开(公告)日：2009-12-31
申请号：US12281197
申请日：2007-02-23
申请人： Zeling Cai , Ann Moriarty , Per A. Peterson , Jon M. Richards
发明人： Zeling Cai , Ann Moriarty , Per A. Peterson , Jon M. Richards
CPC分类号： A61K39/0011 , A61K35/17 , A61K38/2013 , A61K38/212 , A61K2039/5154 , A61K2039/5158 , A61K2039/55522 , A61K2039/55533 , A61K2300/00
摘要： In a cancer treatment combining cell therapy with chemotherapy, autologous CD8+ T cells are obtained from a patient, activated ex vivo by contacting them with xenogenic antigen presenting cells loaded with selected peptide antigen, thereby generating antigen-specific activated cytotoxic T lymphocytes. Such activated CTLs are administered to the patient in conjunction with a lymphodepletion and CTL maintenance regimen comprising a non-myeloblative but lymphdepleting agent, such as cladribine or denileukin diftitox, and interleukin-2 and interferon-α-2b stimulatory cytokines.
摘要翻译： 在结合细胞治疗与化疗的癌症治疗中，从患者获得自体CD8 + T细胞，通过将它们与负载选择的肽抗原的异种抗原呈递细胞接触，从而离体活化，从而产生抗原特异性激活的细胞毒性T淋巴细胞。 这种活化的CTL与淋巴结清除和CTL维持方案一起施用于患者，所述方法包括非球形性但淋巴结清除剂，例如克拉屈滨或denileukin diftitox，以及白细胞介素-2和干扰素-α-2b刺激性细胞因子。
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4.发明授权公开(公告)号：US07993638B2
公开(公告)日：2011-08-09
申请号：US12281197
申请日：2007-02-23
申请人： Zeling Cai , Ann Moriarty , Per A. Peterson , Jon M. Richards
发明人： Zeling Cai , Ann Moriarty , Per A. Peterson , Jon M. Richards
CPC分类号： A61K39/0011 , A61K35/17 , A61K38/2013 , A61K38/212 , A61K2039/5154 , A61K2039/5158 , A61K2039/55522 , A61K2039/55533 , A61K2300/00
摘要： In a cancer treatment combining cell therapy with chemotherapy, autologous CD8+ T cells are obtained from a patient, activated ex vivo by contacting them with xenogenic antigen presenting cells loaded with selected peptide antigen, thereby generating antigen-specific activated cytotoxic T lymphocytes. Such activated CTLs are administered to the patient in conjunction with a lymphodepletion and CTL maintenance regimen comprising a non-myeloblative but lymphdepleting agent, such as cladribine or denileukin diftitox, and interleukin-2 and interferon-α-2b stimulatory cytokines.
摘要翻译： 在结合细胞治疗与化疗的癌症治疗中，从患者获得自体CD8 + T细胞，通过将它们与负载选择的肽抗原的异种抗原呈递细胞接触，从而离体活化，从而产生抗原特异性激活的细胞毒性T淋巴细胞。 结合淋巴滤除和CTL维持方案向患者施用这种活化的CTL，其包括非球形性但淋巴结清除剂，例如克拉屈滨或denileukin diftitox，以及白细胞介素-2和干扰素-α-2b刺激性细胞因子。
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