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11. 发明授权

US08323965B2 Identification of antigenic peptides from multiple myeloma cells 有权
公开(公告)号：US08323965B2
公开(公告)日：2012-12-04
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： C12N5/00 , C12N5/08
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.

12. 发明授权

US08106153B2 Ex-vivo priming for generating cytotoxic T lymphocytes specific for non-tumor antigens to treat autoimmune and allergic disease 有权
公开(公告)号：US08106153B2
公开(公告)日：2012-01-31
申请号：US12892068
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： A61K38/00
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.

13. 发明授权

US08084253B2 Ex-vivo priming for generating cytotoxic T lymphocytes specific for non-tumor antigens to treat autoimmune and allergic disease 有权
公开(公告)号：US08084253B2
公开(公告)日：2011-12-27
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： C12N5/02 , C12N5/06
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.

14. 发明申请

US20110065187A1 EX-VIVO PRIMING FOR GENERATING CYTOTOXIC T LYMPHOCYTES SPECIFIC FOR NON-TUMOR ANTIGENS TO TREAT AUTOIMMUNE AND ALLERGIC DISEASE 有权
公开(公告)号：US20110065187A1
公开(公告)日：2011-03-17
申请号：US12899069
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.

15. 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。

16. 发明授权

US08357533B2 Preparation of inactivated artificial antigen presenting cells and their use in cell therapies 有权
公开(公告)号：US08357533B2
公开(公告)日：2013-01-22
申请号：US13350085
申请日：2012-01-13
申请人： Zeling Cai , Ann Moriarty , Juli Degraw , Didier Leturcq , Wei-Xing Shi , Karen Kabat Stegman , Xilian Yue
发明人： Zeling Cai , Ann Moriarty , Juli Degraw , Didier Leturcq , Wei-Xing Shi , Karen Kabat Stegman , Xilian Yue
IPC分类号： C12N5/10
CPC分类号： A61K39/0011 , A61K2039/5154 , A61K2039/5158 , C12N5/0636 , C12N5/0639
摘要： Methods of processing inactivated artificial antigen presenting cells (aAPCs) and artificial antigen presenting cells with specificity for selected antigenic peptides are described, including their generation and use in cell therapy compositions comprising activated cytotoxic T lymphocytes. Inactivated aAPCs are advantageously generated through crosslinking, such as via a photoreaction involving a psoralen derivative and UVA irradiation.

17. 发明授权

US08133728B2 Ex-vivo priming for generating cytotoxic T lymphocytes specific for non-tumor antigens to treat autoimmune and allergic disease 有权
公开(公告)号：US08133728B2
公开(公告)日：2012-03-13
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： 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.

18. 发明授权

US08133726B2 Ex-vivo priming for generating cytotoxic T lymphocytes specific for non-tumor antigens to treat autoimmune and allergic disease 有权
标题翻译：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：US08133726B2
公开(公告)日：2012-03-13
申请号：US12899069
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： C12N5/08
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。

19. 发明申请

US20120045466A1 IDENTIFICATION OF ANTIGENIC PEPTIDES FROM MULTIPLE MYELOMA CELLS 有权
标题翻译：鉴定来自多个MYELOMA细胞的抗原肽
公开(公告)号：US20120045466A1
公开(公告)日：2012-02-23
申请号：US13285517
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： A61K39/00 , A61P35/00 , A61P37/04 , C07K7/06
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.
摘要翻译：多发性骨髓瘤（MM）是克隆性B细胞恶性肿瘤，并且通过常规抗肿瘤治疗基本上不能治愈。 MM患者的中位生存期仅为3年。 MM的特征在于骨髓（BM）中成熟浆细胞的增殖和积累，导致骨破坏，BM衰竭，贫血和免疫功能降低。在多发性骨髓瘤细胞上呈现MHC I类HLA-A2，相关肽的鉴定是开发MM免疫疗法的重要一步。这里提出的是产生对加载肽的T2靶细胞和多发性骨髓瘤细胞系具有细胞毒性的活化的T淋巴细胞的方法。

20. 发明授权

US08075895B2 Identification of antigenic peptides from multiple myeloma cells 有权
标题翻译：鉴定多发性骨髓瘤细胞的抗原肽
公开(公告)号：US08075895B2
公开(公告)日：2011-12-13
申请号：US12564501
申请日：2009-09-22
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： A61K39/00 , C07K14/00
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.
摘要翻译：多发性骨髓瘤（MM）是克隆性B细胞恶性肿瘤，并且通过常规抗肿瘤治疗基本上不能治愈。 MM患者的中位生存期仅为3年。 MM的特征在于骨髓（BM）中成熟浆细胞的增殖和积累，导致骨破坏，BM衰竭，贫血和免疫功能降低。在多发性骨髓瘤细胞上呈现MHC I类HLA-A2，相关肽的鉴定是开发MM免疫疗法的重要一步。这里提出的是产生对加载肽的T2靶细胞和多发性骨髓瘤细胞系具有细胞毒性的活化的T淋巴细胞的方法。

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