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1. 发明申请

WO2011037859A2 IDENTIFICATION OF ANTIGENIC PEPTIDES FROM MULTIPLE MYELOMA CELLS 审中-公开
标题翻译：从多种MYELOMA细胞鉴定抗原肽
公开(公告)号：WO2011037859A2
公开(公告)日：2011-03-31
申请号：PCT/US2010049466
申请日：2010-09-20
申请人： JANSSEN PHARMACEUTICA NV , ZELING CAI , SHI WEI-XING , LIU XUEJUN P , WU JIEJUN
发明人： ZELING CAI , SHI WEI-XING , LIU XUEJUN P , WU JIEJUN
IPC分类号： A61K38/20 , A61K38/08 , A61K38/10 , C07K7/06 , C07K7/08
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.
摘要翻译：多发性骨髓瘤（MM）是一种克隆性B细胞恶性肿瘤，通过常规的抗肿瘤治疗基本上无法治愈。 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。

2. 发明申请

WO2011037859A3 IDENTIFICATION OF ANTIGENIC PEPTIDES FROM MULTIPLE MYELOMA CELLS 审中-公开
标题翻译：从多种骨髓细胞中鉴定抗原肽
公开(公告)号：WO2011037859A3
公开(公告)日：2011-03-31
申请号：PCT/US2010/049466
申请日：2010-09-20
申请人： JANSSEN PHARMACEUTICA NV , ZELING, Cai , SHI, Wei-Xing , LIU, Xuejun, P. , WU, Jiejun
发明人： ZELING, Cai , SHI, Wei-Xing , LIU, Xuejun, P. , WU, Jiejun
IPC分类号： C07K7/00 , A61K39/00
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B细胞恶性肿瘤，并且通过传统的抗肿瘤治疗基本上不可治愈。 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，骨髓衰竭，贫血和免疫功能降低。在多发性骨髓瘤细胞上呈递的MHC I类，HLA-A2相关肽的鉴定是开发MM的免疫疗法中的重要步骤。这里展示的是用于产生活化的T淋巴细胞的方法，所述活化的T淋巴细胞对装载肽的T2靶细胞和多发性骨髓瘤细胞系都是细胞毒性的。

3. 发明授权

US08323655B2 Identification of antigenic peptides from multiple myeloma cells 有权
公开(公告)号：US08323655B2
公开(公告)日：2012-12-04
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 , 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.

4. 发明授权

US08232101B2 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：US08232101B2
公开(公告)日：2012-07-31
申请号：US13285459
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 , A61K38/00 , 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。

5. 发明申请

US20120115223A1 PREPARATION OF INACTIVATED ARTIFICIAL ANTIGEN PRESENTING CELLS AND THEIR USE IN CELL THERAPIES 有权
标题翻译：灭活人工抗原呈递细胞的制备及其在细胞治疗中的应用
公开(公告)号：US20120115223A1
公开(公告)日：2012-05-10
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.
摘要翻译：描述了处理灭活的人抗原呈递细胞（aAPCs）和对所选抗原肽具有特异性的人造抗原呈递细胞的方法，包括其在包含活化的细胞毒性T淋巴细胞的细胞治疗组合物中的产生和使用。非活化的aAPC有利地通过交联产生，例如通过涉及补骨脂素衍生物和UVA照射的光反应。

6. 发明授权

US08084256B2 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：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。

7. 发明授权

US07993638B2 Cancer treatment combining lymphodepleting agent with CTLs and cytokines 有权
标题翻译：结合淋巴细胞凋亡剂与CTL和细胞因子的癌症治疗
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
IPC分类号： A61K38/19 , A61K38/20 , A61K38/21 , A61K35/12
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。

8. 发明申请

US20060234310A1 Enriched antigen-specific T-cells and related therapeutic and prophylactic compositions and methods 审中-公开
标题翻译：富含抗原特异性T细胞及相关治疗和预防组合物和方法
公开(公告)号：US20060234310A1
公开(公告)日：2006-10-19
申请号：US11415135
申请日：2006-05-01
申请人： Zeling Cai , Michael Jackson , Homero Sepulveda , Jing-Feng Huang
发明人： Zeling Cai , Michael Jackson , Homero Sepulveda , Jing-Feng Huang
IPC分类号： G01N33/567 , G01N33/53
CPC分类号： G01N33/56972 , G01N33/5005 , G01N33/505 , G01N33/56977
摘要： T-cell responses are initiated via contact with MHC/peptide complexes on antigen presenting cells (APCs). The fate of these complexes, however, is unknown. Here, using live APCs expressing MHC class I molecules fused with green-fluorescent protein, we show that peptide-specific T-cell/APC interaction induces clusters of MHC I molecules to congregate within minutes at the contact site; thereafter, these MHC I clusters are acquired by T-cells in small aggregates.,We further demonstrate that acquisition of MHC I by T-cells correlates with TCR down regulation and the APC-derived MHC I molecules are endocytosed and degraded by-T-cells. These data suggest a novel mechanism by which TCR recognition of MHC/peptide complexes can be curtailed by internalization of MHC molecules by T-cells.
摘要翻译：通过与抗原呈递细胞（APC）上的MHC /肽复合物接触来启动T细胞应答。然而，这些复合体的命运是未知的。在这里，使用表达与绿色荧光蛋白融合的MHC I类分子的活APCs，我们显示肽特异性T细胞/ APC相互作用诱导MHC I分子簇在接触部位几分钟内聚集; 此后，这些MHC I簇由小的聚集体中的T细胞获得，我们进一步证明，T细胞的MHC I的获得与TCR下调相关，APC衍生的MHC I分子被胞吞并被-T- 细胞。这些数据表明可以通过T细胞的MHC分子的内化来减少MHC /肽复合物的TCR识别的新机制。

9. 发明申请

US20050152916A1 Antigen presenting system and methods for activation of T-cells 审中-公开
标题翻译：抗原呈递系统和激活T细胞的方法
公开(公告)号：US20050152916A1
公开(公告)日：2005-07-14
申请号：US11005750
申请日：2004-12-07
申请人： Zeling Cai , Jonathan Sprent , Anders Brunmark , Michael Jackson , Per Peterson , Alain Luxembourg , Didier Leturcq , Ann Moriarty
发明人： Zeling Cai , Jonathan Sprent , Anders Brunmark , Michael Jackson , Per Peterson , Alain Luxembourg , Didier Leturcq , Ann Moriarty
IPC分类号： C12N15/09 , A61K35/14 , A61K38/00 , A61K39/00 , A61K48/00 , A61P35/00 , C07K14/025 , C07K14/145 , C07K14/705 , C07K14/74 , C12N5/07 , C12N5/0783 , C12N5/10 , C12N15/12 , C12N15/85 , C12P21/02
CPC分类号： C12N5/0601 , A61K38/00 , A61K2039/5158 , C07K14/005 , C07K14/70503 , C07K14/70539 , C12N5/0636 , C12N15/85 , C12N2501/50 , C12N2501/51 , C12N2502/50 , C12N2502/99 , C12N2760/16122 , C12N2760/18822 , C12N2760/20222 , C12N2830/002 , C12N2830/75 , C12N2830/80 , Y10S530/812 , Y10S530/827
摘要： The present invention relates to synthetic antigen-presenting matrices, their methods of making and their methods of use. One such matrix is cells that have been transfected to produce MHC antigen-presenting molecules and assisting molecules such as co-stimulatory molecules. The matrices can be used to activate CD8+ T-cells to produce cytokines and become cytotoxic.
摘要翻译：本发明涉及合成抗原呈递矩阵，其制备方法及其使用方法。一种这样的基质是已被转染以产生MHC抗原呈递分子并辅助分子如共刺激分子的细胞。该基质可用于激活CD8 + T细胞以产生细胞因子并变成细胞毒性。

10. 发明申请

US20200262921A1 CTLA-4 ANTIBODIES AND USES THEREOF 审中-公开
公开(公告)号：US20200262921A1
公开(公告)日：2020-08-20
申请号：US15777369
申请日：2015-11-19
申请人： Zeling Cai , Yi Chen
发明人： Zeling Cai , Yi Chen
IPC分类号： C07K16/28 , A61K39/395 , A61K39/00 , A61K39/29
摘要： Human antibodies which specifically bind to human CTLA-4, and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

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