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公开(公告)号：US4844893A
公开(公告)日：1989-07-04
申请号：US916173
申请日：1986-10-07
申请人： Cyril J. Honsik , Ralph A. Reisfeld
发明人： Cyril J. Honsik , Ralph A. Reisfeld
CPC分类号： A61K47/48369 , Y10S424/804 , Y10S530/808 , Y10S530/828
摘要： A method and composition for killing target cells is disclosed. The method utilizes ex vivo IL-2 activation of leucocyte effector cells and arming the activated leucocyte effectors with monoclonal antibodies whose Fc portions bind to the IL-2-activated effectors and whose paratopic portions immunoreact with an epitope expressed on the surfaces of the target cells. The composition contains a cytolytic amount of the armed, IL-2-activated effector cells dispersed in an aqueous physiologically tolerable diluent medium.
摘要翻译： 公开了一种杀死靶细胞的方法和组合物。 该方法利用白细胞效应细胞的离体IL-2激活和用Fc部分结合IL-2活化的效应物并且其互补部分与靶细胞表面上表达的表位免疫反应的单克隆抗体来装备活化的白细胞效应子 。 组合物含有分散在水性生理上可耐受的稀释培养基中的溶解量的经驱动的IL-2活化的效应细胞。
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公开(公告)号：US09616137B2
公开(公告)日：2017-04-11
申请号：US13224399
申请日：2011-09-02
申请人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo , Debbie Liao , Ze Liu , Tingmei Chen , Si Chen , Dan Lu
发明人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo , Debbie Liao , Ze Liu , Tingmei Chen , Si Chen , Dan Lu
CPC分类号： A61K31/58 , A61K9/127 , A61K9/1271 , A61K9/1272 , A61K31/4164 , A61K31/704 , A61K47/28 , A61K47/6911 , A61K47/6913 , B82Y5/00
摘要： The present invention provides an aqueous tumor-targeting liposome nanoparticle composition comprising an aqueous dispersion of liposome nanoparticles. The nanoparticles preferably encapsulate an anti-cancer chemotherapeutic agent, which can be added to a pre-formed liposome composition or can be incorporated in the liposomes during the formation of the liposomes. The liposome nanoparticles comprise a legumain-targeting lipid admixed with one or more other micelle or vesicle-forming lipid materials in the form of nanoparticulate liposomes dispersed in an aqueous carrier. A preferred tumor-targeting liposome nanoparticle composition comprises (a) a legumain-targeting lipid component, (b) a zwitterionic lipid component; (c) an amino-substituted lipid component; (d) a neutral lipid component; and (e) polyethylene glycol-conjugated lipid component. The legumain-targeting lipid component comprising a hydrophobic lipid portion covalently attached to a legumain-binding moiety.
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3.发明授权DNA composition encoding an immunogenic VEGF receptor peptide and methods of use thereof 有权编码免疫原性VEGF受体肽的DNA组合物及其使用方法公开(公告)号：US08241637B2
公开(公告)日：2012-08-14
申请号：US13280855
申请日：2011-10-25
CPC分类号： A61K39/0005 , A61K39/0011 , A61K2039/522 , A61K2039/53 , A61K2039/542 , Y02A50/484
摘要： A method of inhibiting endothelial cell proliferation in a mammal is provided. The method comprises the step of administering to the mammal an effective immunological response eliciting amount of a DNA composition comprising a DNA construct operably encoding a VEGF receptor polypeptide and a pharmaceutically acceptable carrier therefor, whereby said mammal exhibits an immune response elicited by vaccine and specific to proliferating endothelial cells. The methods of this invention inhibit vascular endothelial cell proliferation in the tumor micro-environment. Angiogenesis inhibition and subsequent decrease in tumor growth and dissemination is achieved.
摘要翻译： 提供了抑制哺乳动物内皮细胞增殖的方法。 该方法包括向哺乳动物施用有效的免疫应答引发量的DNA组合物的步骤，该组合物包含可操作地编码VEGF受体多肽的DNA构建体及其药学上可接受的载体，由此所述哺乳动物表现出由疫苗引起的免疫应答， 增殖性内皮细胞。 本发明的方法抑制肿瘤微环境中的血管内皮细胞增殖。 实现血管发生抑制和随后肿瘤生长和传播的减少。
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4.发明授权DNA composition encoding an immunogenic VEGF receptor peptide and methods of use thereof 有权编码免疫原性VEGF受体肽的DNA组合物及其使用方法公开(公告)号：US08048428B2
公开(公告)日：2011-11-01
申请号：US11507298
申请日：2006-08-21
CPC分类号： A61K39/0005 , A61K39/0011 , A61K2039/522 , A61K2039/53 , A61K2039/542 , Y02A50/484
摘要： A DNA composition effective for inhibiting endothelial cell proliferation comprises a DNA construct operably encoding a vascular endothelial growth factor (VEGF) receptor polypeptide, which can be a full length VEGF receptor protein or an immunogenic fragment thereof. This invention provides DNA compositions that encode VEGF receptor-2 (KDR), VEGF receptor-1 (Flt-1), or Flk-1 (the murine homolog of KDR), as well as methods of using such a DNA composition to inhibit vascular endothelial cell proliferation in the tumor micro-environment. Angiogenesis inhibition and subsequent decrease in tumor growth and dissemination is achieved.
摘要翻译： 有效抑制内皮细胞增殖的DNA组合包括可操作地编码血管内皮生长因子（VEGF）受体多肽的DNA构建体，其可以是全长VEGF受体蛋白质或其免疫原性片段。 本发明提供编码VEGF受体-2（KDR），VEGF受体-1（Flt-1）或Flk-1（KDR的鼠同源物）的DNA组合物，以及使用这种DNA组合物抑制血管的方法 内皮细胞增殖在肿瘤微环境中。 实现血管发生抑制和随后肿瘤生长和传播的减少。
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5.发明授权Methods for treatment of tumors and metastases using a combination of anti-angiogenic and immuno therapies 有权使用抗血管生成和免疫疗法的组合治疗肿瘤和转移的方法公开(公告)号：US07365054B2
公开(公告)日：2008-04-29
申请号：US11527029
申请日：2006-09-26
IPC分类号： A61K38/00
CPC分类号： C07K7/64 , A61K38/00 , A61K38/19 , A61K38/2013 , A61K39/395 , A61K45/06 , A61K47/6813 , A61K2300/00
摘要： The invention provides methods for treating tumors and tumor metastases in a mammal comprising administering, to a mammal in need of treatment, a therapeutic amount of an antagonist sufficient to inhibit angiogenesis in combination with a therapeutic amount of anti-tumor immunotherapeutic agent, such as a anti-tumor antigen antibody/cytokine fusion protein having a cytokine and a recombinant immunoglobulin polypeptide chain sufficient to elicit a cytokine-specific biological response.
摘要翻译： 本发明提供了治疗哺乳动物肿瘤和肿瘤转移的方法，包括向需要治疗的哺乳动物施用治疗量足以抑制血管生成的拮抗剂与治疗量的抗肿瘤免疫治疗剂（例如 抗肿瘤抗原抗体/细胞因子融合蛋白，其具有足以引发细胞因子特异性生物反应的细胞因子和重组免疫球蛋白多肽链。
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公开(公告)号：US09629922B2
公开(公告)日：2017-04-25
申请号：US13820413
申请日：2011-09-02
申请人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo , Debbie Liao , Ze Liu , Tingmei Chen , Si Chen , Dan Lu
发明人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo , Debbie Liao , Ze Liu , Tingmei Chen , Si Chen , Dan Lu
CPC分类号： A61K31/58 , A61K9/127 , A61K9/1271 , A61K9/1272 , A61K31/4164 , A61K31/704 , A61K47/28 , A61K47/6911 , A61K47/6913 , B82Y5/00
摘要： The present invention provides an aqueous tumor-targeting liposome nanoparticle composition comprising an aqueous dispersion of liposome nanoparticles. The nanoparticles preferably encapsulate an anti-cancer chemotherapeutic agent, which can be added to a pre-formed liposome composition or can be incorporated in the liposomes during the formation of the liposomes. The liposome nanoparticles comprise a legumain-targeting lipid admixed with one or more other micelle or vesicle-forming lipid materials in the form of nanoparticulate liposomes dispersed in an aqueous carrier. A preferred tumor-targeting liposome nanoparticle composition comprises (a) a legumain-targeting lipid component, (b) a zwitterionic lipid component; (c) an amino-substituted lipid component; (d) a neutral lipid component; and (e) polyethylene glycol-conjugated lipid component. The legumain-targeting lipid component comprising a hydrophobic lipid portion covalenetly attached to a legumain-binding moiety.
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7.发明授权Methods for treatment of tumors and metastases using a combination of anti-angiogenic and immuno therapies 有权使用抗血管生成和免疫疗法的组合治疗肿瘤和转移的方法公开(公告)号：US07115261B1
公开(公告)日：2006-10-03
申请号：US09502732
申请日：2000-02-11
IPC分类号： A61K38/00 , A61K39/395 , A61K38/19
CPC分类号： C07K7/64 , A61K38/00 , A61K38/19 , A61K38/2013 , A61K39/395 , A61K45/06 , A61K47/6813 , A61K2300/00
摘要： The invention teaches methods for treating tumors and tumor metastases in a mammal comprising administering, to a mammal in need of treatment, a therapeutic amount of an antagonist sufficient to inhibit angiogenesis in combination with a therapeutic amount of anti-tumor immunotherapeutic agent, such as a anti-tumor antigen antibody/cytokine fusion protein having a cytokine and a recombinant immunoglobulin polypeptide chain sufficient to elicit a cytokine-specific biological response.
摘要翻译： 本发明教导了用于治疗哺乳动物的肿瘤和肿瘤转移的方法，其包括向需要治疗的哺乳动物施用治疗量的足以抑制血管发生的拮抗剂与治疗量的抗肿瘤免疫治疗剂（例如 抗肿瘤抗原抗体/细胞因子融合蛋白，其具有足以引发细胞因子特异性生物反应的细胞因子和重组免疫球蛋白多肽链。
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公开(公告)号：US06923958B2
公开(公告)日：2005-08-02
申请号：US10090238
申请日：2002-03-02
申请人： Rong Xiang , Ralph A. Reisfeld
发明人： Rong Xiang , Ralph A. Reisfeld
IPC分类号： C12N15/09 , A61J1/14 , A61K35/74 , A61K35/76 , A61K38/00 , A61K39/00 , A61K39/39 , A61K48/00 , A61P35/00 , C07K14/705 , C12N15/12 , C12N15/19 , C12N15/63 , A01N48/00 , C12N15/75 , C12N15/79 , C12P19/34
CPC分类号： A61K39/0011 , A61K2039/522 , A61K2039/523 , A61K2039/53 , A61K2039/55516 , A61K2039/55533 , C07K14/70503 , C07K14/70575
摘要： A DNA vaccine effective for eliciting an immune response against cells that present a carcinoembryonic antigen (CEA) comprises a DNA operably encoding a CEA and a DNA operably encoding a CD40 ligand, SEQ ID NO:1 and SEQ ID NO: 2, respectively, or its homotrimer, CD40LT. The DNA vaccine can be incorporated in a delivery vector such as an attenuated live bacterium or virus, or a liposome carrier. In a method embodiment, the DNA vaccine is administered orally to a mammal, such as a human, to elicit an immune response against CEA presenting cells such as colon cancer cells. A preferred method embodiment includes the additional step of treating the mammal with recombinant antibody fusion protein huKS1/4-IL2 to enhance the immune response effectiveness of the vaccine.
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公开(公告)号：US4675287A
公开(公告)日：1987-06-23
申请号：US634687
申请日：1984-07-26
申请人： Ralph A. Reisfeld , Gregor Schulz
发明人： Ralph A. Reisfeld , Gregor Schulz
IPC分类号： G01N33/577 , A61K38/00 , A61K39/00 , C07K1/22 , C07K14/005 , C07K14/195 , C07K16/00 , C07K16/30 , C07K19/00 , C12N5/00 , C12N15/00 , C12N15/02 , C12P5/00 , C12P21/00 , C12P21/08 , C12R1/91 , G01N33/53 , G01N33/544
CPC分类号： C07K16/30 , A61K38/00 , Y10S435/948 , Y10S435/975 , Y10S436/813 , Y10S530/808 , Y10S530/809 , Y10S530/866
摘要： A non-human, mammalian monoclonal receptor produced and secreted by a hybridoma having the ATCC accession number HB 8568 and methods of preparing and using same, as well as diagnostics utilizing the receptor are disclosed. The monoclonal receptor reacts with cells such as human neuroectodermal tumors having ganglioside GD.sub.2 antigen expressed on their cellular membrane surfaces.
摘要翻译： 公开了由具有ATCC登录号HB 8568的杂交瘤产生和分泌的非人哺乳动物单克隆受体及其制备和使用方法，以及利用该受体的诊断。 单克隆受体与细胞例如在其细胞膜表面上表达神经节苷脂GD2抗原的人类神经外胚层肿瘤反应。
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公开(公告)号：US08716254B2
公开(公告)日：2014-05-06
申请号：US10807897
申请日：2004-03-24
申请人： Rong Xiang , He Zhou , Ralph A. Reisfeld
发明人： Rong Xiang , He Zhou , Ralph A. Reisfeld
CPC分类号： A61J1/05 , A61K6/00 , A61K39/0011 , A61K2039/523 , A61K2039/53 , A61K2039/55516 , A61K2039/55522 , Y02A50/484
摘要： A DNA vaccine suitable for eliciting an immune response against cancer cells comprises a DNA construct operably encoding a cancer-associated Inhibitor of Apoptosis-family protein and an immunoactive gene product, such as a cytokine or a ligand for a natural killer cell surface receptor, in a pharmaceutically acceptable carrier. A preferred cytokine is CCL21. Preferred ligands for a natural killer cell surface receptor include human MICA, human MICB, human ULBP1, human ULBP2, and human ULBP3. The cancer-associated Inhibitor of Apoptosis (IAP)-family protein is preferably a survivin protein or livin protein. Method of inhibiting tumor growth by administering the vaccine of the invention to a mammal is also described.
摘要翻译： 适用于引发针对癌细胞的免疫应答的DNA疫苗包括可操作地编码癌相关的凋亡家族蛋白抑制剂的DNA构建体和免疫活性基因产物，例如细胞因子或天然杀伤细胞表面受体的配体， 药学上可接受的载体。 优选的细胞因子是CCL21。 用于天然杀伤细胞表面受体的优选配体包括人MICA，人MICB，人ULBP1，人ULBP2和人ULBP3。 癌症相关的凋亡抑制剂（IAP）家族蛋白质优选是存活蛋白质蛋白质或livin蛋白质。 还描述了通过将哺乳动物施用本发明的疫苗来抑制肿瘤生长的方法。
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