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1. 发明申请

WO03010292A3 METHODS AND APPARATUS FOR ENRICHMENT AND CULTURE OF MONOCYTIC DENDRITIC CELL PRECURSORS 审中-公开
标题翻译：单细胞细胞前体培养和培养的方法和装置
公开(公告)号：WO03010292A3
公开(公告)日：2003-05-22
申请号：PCT/US0223865
申请日：2002-07-25
申请人： NORTHWEST BIOTHERAPEUTICS INC , BOSCH MARNIX L , TJOA BENJAMIN A , HARRIS PAUL C
发明人： BOSCH MARNIX L , TJOA BENJAMIN A , HARRIS PAUL C
IPC分类号： C12M1/16 , C12N5/00 , C12N5/0784 , G01N33/50 , G01N33/569
CPC分类号： C12N5/0087 , C12N5/0639 , C12N2501/22 , C12N2501/23 , G01N33/5005 , G01N33/56972
摘要： The present invention provides methods and materials for isolating, culturing and differentiating monocytic dendritic cell precursors to form immature and/or mature dendritic cells. In a related aspect, methods, materials, and a system are provided for isolating, culturing and differentiating monocytic dendritic cell precursors under aseptic conditions to obtain immature and/or mature dendritic cells.
摘要翻译：本发明提供用于分离，培养和分化单核细胞树突细胞前体以形成未成熟和/或成熟树突状细胞的方法和材料。在相关方面，提供了方法，材料和系统用于在无菌条件下分离，培养和分化单核细胞树突细胞前体以获得未成熟和/或成熟的树突状细胞。

2. 发明申请

WO2004076651A3 GENERATION OF DENDRITIC CELLS FROM MONOCYTIC DENDRITIC PRECURSOR CELLS WITH GM-CSF IN THE ABSENCE OF ADDITIONAL CYTOKINES 审中-公开
标题翻译：在含有GM-CSF的单核细胞前体细胞中产生增殖细胞因子
公开(公告)号：WO2004076651A3
公开(公告)日：2005-03-10
申请号：PCT/US2004006119
申请日：2004-02-27
申请人： NORTHWEST BIOTHERAPEUTICS INC , TJOA BENJAMIN A , BOSCH MARNIX L
发明人： TJOA BENJAMIN A , BOSCH MARNIX L
IPC分类号： C12N20060101 , C12N5/00 , C12N5/02 , C12N5/0784
CPC分类号： C12N5/0639 , C12N2500/10 , C12N2500/30 , C12N2500/72 , C12N2500/90 , C12N2501/22 , C12N2501/23 , C12N2501/24 , C12N2502/70 , C12N2533/12
摘要： The present invention it was determined that dendritic cells could be derived from various sources including peripheral blood monocytes in the presence of only GM-CSF without other cytokines if the monocytes were not activated. By preventing activation, such as by preventing binding of the cells to the surface of the culture vessel, the monocytes do not require the presence of additional cytokines, such as IL-4 or IL-13, to prevent differentiation into a non-dendritic cell lineage. The immature DCs generated and maintained in this manner were CD14 and expressed high levels of CD1a. Upon maturation by contact with an agent such as, for example, BCG and IFNgamma, the cells were determined to express surface molecules typical of mature dendritic cells purified by prior methods and cultured in the presence of GM-CSF and IL-4. The mature dendritic cells produced from monoxytes without activation and cultured in GM-CSF alone are suitable for use in dendritic cell-based immunotherapy methods, such as for use in the treatment of disease, including cancer.
摘要翻译：本发明确定如果单核细胞未被激活，则在存在只有GM-CSF的情况下，树突状细胞可以来源于各种来源，包括外周血单核细胞。通过防止活化，例如通过防止细胞与培养容器表面的结合，单核细胞不需要另外的细胞因子如IL-4或IL-13的存在，以防止分化成非树突状细胞血统。以这种方式产生和维持的未成熟DCs是CD14 - 并且表达高水平的CD1a。通过与例如BCG和IFNγ的试剂接触成熟，测定细胞表达通过现有方法纯化并在GM-CSF和IL-4存在下培养的成熟树突状细胞的典型表达分子。由单核细胞产生的成熟树突状细胞无活化并单独在GM-CSF中培养，适用于树突细胞基免疫治疗方法，例如用于治疗包括癌症在内的疾病。

3. 发明专利

AU2003243673A1 TANGENTIAL FLOW FILTRATION DEVICES AND METHODS FOR LEUKOCYTE ENRICHMENT 未知
公开(公告)号：AU2003243673A1
公开(公告)日：2004-01-06
申请号：AU2003243673
申请日：2003-06-19
申请人： LODGE PATRICIA A , NORTHWEST BIOTHERAPEUTICS INC , BOSCH MARNIX L , HARRIS PAUL C , MONAHAN STEVEN J , TURNER ALLEN , BOYNTON ALTON L
发明人： LODGE PATRICIA A , BOSCH MARNIX L , HARRIS PAUL C , MONAHAN STEVEN J , TURNER ALLEN , BOYNTON ALTON L
IPC分类号： C12M1/26 , A61M1/34 , A61M1/36 , A61M1/38 , B01D61/00 , B01D61/14 , B01D61/16 , B01D61/18 , B01D61/22 , C12M3/00 , C12N5/06
摘要： The present invention provides tangential flow filtration devices and methods for enriching a heterogeneous mixture of blood constituents for leukocytes by removal of non-leukocyte blood constituents. In one particular embodiment the device can provide a composition enriched in monocytes. One embodiment includes a remover unit (1) having a crossflow chamber (3) separated by a microporous filter (5) from a filtrate chamber (4), the remover unit (1) also having a tangential flow inlet (6), a fluid outlet (7) for a fluid enriched in leukocytes and a filtrate outlet (8).

4. 发明申请

WO2007067782A3 COMPOSITIONS AND METHODS FOR INDUCING THE ACTIVATION OF IMMATURE MONOCYTIC DENDRITIC CELLS 审中-公开
标题翻译：用于诱导轻度单核细胞激活的组合物和方法
公开(公告)号：WO2007067782A3
公开(公告)日：2008-02-14
申请号：PCT/US2006047083
申请日：2006-12-08
申请人： NORTHWEST BIOTHERAPEUTICS INC , BOYNTON ALTON L , BOSCH MARNIX L
发明人： BOYNTON ALTON L , BOSCH MARNIX L
IPC分类号： C12N5/00 , C12N5/0784
CPC分类号： C12N5/0639 , A61K39/0011 , A61K2039/5154 , C12N2501/22 , C12N2501/23
摘要： The present invention provides methods for inducing the maturation of immature dendritic cells (DC) and for activating those cells without the use of a dendritic cell maturation agent. The activated DC can be used for inducing an antigen specific T cell response. Methods of the invention can also comprise the addition of a directional maturation agent, such as interferon gamma, to induce a Th-I and/or Th-2 bias in the response obtained. The present invention also provides dendritic cell populations useful for activating and for inducing antigen specific T cells. Similarly, activated antigen specific T cell populations, and methods of making the same are provided.
摘要翻译：本发明提供了诱导未成熟树突状细胞（DC）的成熟以及在不使用树突状细胞成熟剂的情况下激活那些细胞的方法。活化的DC可用于诱导抗原特异性T细胞应答。本发明的方法还可以包括添加方向成熟剂，例如干扰素γ，以在获得的反应中诱导Th-1和/或Th-2偏倚。本发明还提供了可用于激活和诱导抗原特异性T细胞的树突状细胞群。类似地，提供了活化的抗原特异性T细胞群体及其制备方法。

5. 发明申请

WO2004053072A3 ADMINISTRATION OF DENDRITIC CELLS PARTIALLY MATURED IN VITRO FOR THE TREATMENT OF TUMORS 审中-公开
标题翻译：肿瘤治疗肿瘤部位成形细胞的管理
公开(公告)号：WO2004053072A3
公开(公告)日：2005-06-16
申请号：PCT/US0338672
申请日：2003-12-05
申请人： NORTHWEST BIOTHERAPEUTICS INC , BOSCH MARNIX L
发明人： BOSCH MARNIX L
IPC分类号： A61K39/00 , C12N5/0784 , A61K31/44 , C12N5/00 , C12N5/02 , A61K355/26
CPC分类号： C12N5/0639 , A61K39/0011 , A61K2039/5154 , C12N2500/72 , C12N2501/05 , C12N2501/24
摘要： The present invention provides populations of cells comprising partially matured dendritic cells that can be used for administration individuals having a tumor. Partially matured dendritic cells, those contacted with a dendritic cell maturation agent for about 1 to about 10 hours, or more, efficiently take up and process tumor antigens in the area of the tumor site, complete maturation, and can subsequently migrate to the lymph nodes of a treated individual. Once in the lymph node the now fully mature antigen presenting dendritic cells secrete the appropriate cytokines (e.g., TNFalpha and IL-12) and contact T cells inducing a substantial anti-tumor immune response.
摘要翻译：本发明提供包含部分成熟的树突状细胞的细胞群，其可用于给予具有肿瘤的个体。部分成熟的树突状细胞，与树突状细胞成熟剂接触约1至约10小时或更长时间，有效地占据和处理肿瘤部位的肿瘤抗原，完全成熟，并随后迁移至淋巴结被治疗的个体。一旦在淋巴结中，现在完全成熟的抗原呈递树突状细胞分泌适当的细胞因子（例如TNFα和IL-12）并接触诱导大量抗肿瘤免疫应答的T细胞。

6. 发明专利

JP2011246493A Administration of dendritic cell partially matured in vitro for treatment of tumor 有权
标题翻译：体外治疗肿瘤的局部细胞分泌物的治疗
公开(公告)号：JP2011246493A
公开(公告)日：2011-12-08
申请号：JP2011196385
申请日：2011-09-08
申请人： Northwest Biotherapeutics Inc , ノースウエストバイオセラピューティクス,インコーポレイティド
发明人： BOSCH MARNIX L
IPC分类号： A61K35/26 , A61K35/14 , A61K39/00 , A61K47/22 , A61K47/42 , A61P35/00 , A61P37/04 , C12N5/0784
CPC分类号： C12N5/0639 , A61K39/0011 , A61K2039/5154 , C12N2500/72 , C12N2501/05 , C12N2501/24
摘要： PROBLEM TO BE SOLVED: To provide efficient up take and processing of tumor antigen within a tumor and tumor bed in spite of overall immunosuppressive environment within the tumor.SOLUTION: There are provided populations of cells comprising partially matured dendritic cells that can be used for administration individuals having a tumor. Partially matured dendritic cells, those contacted with a dendritic cell maturation agent for about 1 to about 10 hours, or more, efficiently take up and process tumor antigens in the area of the tumor site, complete maturation, and can subsequently migrate to the lymph nodes of a treated individual. Once in the lymph node, the now fully mature antigen presenting dendritic cells secrete the appropriate cytokines (e.g., TNFalpha and IL-12) and contact T cells inducing a substantial anti-tumor immune response.
摘要翻译：要解决的问题：尽管肿瘤内存在整体免疫抑制环境，但是在肿瘤和肿瘤床内提供有效的上调和加工肿瘤抗原。解决方案：提供包含部分成熟树突状细胞的细胞群，其可用于给予具有肿瘤的个体。部分成熟的树突状细胞，与树突状细胞成熟剂接触约1至约10小时或更长时间，有效地占据和处理肿瘤部位的肿瘤抗原，完全成熟，并随后迁移至淋巴结被治疗的个体。一旦在淋巴结中，现在完全成熟的抗原呈递树突状细胞分泌适当的细胞因子（例如TNFα和IL-12）并接触诱导大量抗肿瘤免疫应答的T细胞。版权所有（C）2012，JPO＆INPIT

7. 发明专利

JP2013223517A Composition and method for inducing activation of immature monocytic dendritic cell 审中-公开
标题翻译：诱导单因素细胞激活的组合物和方法
公开(公告)号：JP2013223517A
公开(公告)日：2013-10-31
申请号：JP2013162033
申请日：2013-08-05
申请人： Northwest Biotherapeutics Inc , ノースウエストバイオセラピューティクス, インコーポレイテッド
发明人： BOYNTON ALTON L , BOSCH MARNIX L
IPC分类号： C12N5/0784 , C12N5/0783
CPC分类号： C12N5/0639 , A61K39/0011 , A61K2039/5154 , C12N2501/22 , C12N2501/23
摘要： PROBLEM TO BE SOLVED: To provide methods for inducing the maturation of immature dendritic cells (DC) and for activating those immature dendritic cells without the use of a dendritic cell maturation factor.SOLUTION: Activated DC can be used for inducing an antigen specific T cell response. Methods of the invention can also comprise the addition of a directional maturation factor, such as interferon gamma, to induce a Th-1 and/or Th-2 bias in the response obtained. The present invention also provides dendritic cell populations useful for activating and for inducing antigen-specific T cells. Similarly, activated antigen-specific T cell populations, and methods for making the same are provided.
摘要翻译：要解决的问题：提供诱导未成熟树突状细胞（DC）成熟和不使用树突状细胞成熟因子激活那些未成熟树突状细胞的方法。解决方案：活化DC可用于诱导抗原特异性T细胞响应。本发明的方法还可以包括添加方向成熟因子，例如干扰素γ，以在获得的应答中诱导Th-1和/或Th-2偏倚。本发明还提供了可用于激活和诱导抗原特异性T细胞的树突状细胞群。类似地，提供了活化的抗原特异性T细胞群体及其制备方法。

8. 发明专利

JP2011188872A Composition and method for priming monocytic dendritic cell and t cell for th-1 response 有权
标题翻译：用于促进TH-1反应的单核细胞和细胞的组合物和方法
公开(公告)号：JP2011188872A
公开(公告)日：2011-09-29
申请号：JP2011148711
申请日：2011-07-04
申请人： Northwest Biotherapeutics Inc , ノースウエストバイオセラピューティクス,インコーポレイティド
发明人： BOSCH MARNIX L
IPC分类号： C12N5/0784 , A01N63/00 , A61K35/12 , A61K35/14 , A61K39/00 , A61K39/39 , A61K45/00 , A61P37/04 , C07K14/57 , C12N20060101 , C12N5/00 , C12N5/02 , G06K19/00
CPC分类号： C12N5/0639 , A61K2039/5154 , A61K2039/5158 , A61K2039/55522 , A61K2039/55594 , A61K2039/57 , C07K14/5428 , C07K14/5434 , C12N2500/72 , C12N2501/24
摘要： PROBLEM TO BE SOLVED: To provide compositions and methods for inducing maturation of immature dendritic cells (DC) and for priming those cells for inducing a type 1 immune response.
SOLUTION: The present invention also provides dendritic cell populations useful for activating and for preparing T cells polarized towards production of type 1 cytokines and/or a type 1 response. Similarly, activated, polarized T cell populations, and methods of making the same are provided. A method for producing a mature dendritic cell population includes: a step of providing immature dendritic cells; and a step of contacting the immature dendritic cells with an effective amount of BCG and Interferon γ (IFNγ) under culture conditions suitable for maturation of the immature dendritic cells to form the mature dendritic cell population.
COPYRIGHT: (C)2011,JPO&INPIT
摘要翻译：待解决的问题：提供用于诱导未成熟树突状细胞（DC）成熟并用于引发那些细胞以诱导1型免疫应答的组合物和方法。解决方案：本发明还提供可用于激活和制备向1型细胞因子生产和/或1型反应产生极化的T细胞的树突状细胞群。类似地，提供了活化的，极化的T细胞群体及其制备方法。一种生产成熟树突状细胞群的方法包括：提供未成熟树突状细胞的步骤; 以及在适合未成熟树突状细胞成熟的培养条件下使未成熟树突状细胞与有效量的BCG和干扰素γ（IFNγ）接触以形成成熟树突状细胞群的步骤。版权所有（C）2011，JPO＆INPIT

9. 发明专利

JP2011182803A Tangential flow filtration device and method for stem cell enrichment 有权
标题翻译：用于干细胞增殖的过滤流过滤装置和方法
公开(公告)号：JP2011182803A
公开(公告)日：2011-09-22
申请号：JP2011143589
申请日：2011-06-28
申请人： Northwest Biotherapeutics Inc , ノースウエストバイオセラピューティクス,インコーポレイティド
发明人： BOSCH MARNIX L , LODGE PATRICIA A , MCEARCHERN JULIE ANNA , BOYNTON ALTON L , HUGENHOLTZ PAUL G
IPC分类号： C12N5/071 , A61K35/28 , A61P7/00 , A61P9/04 , B01D61/00 , C12M1/12 , C12N5/00 , C12N5/0775 , C12N5/0789
CPC分类号： C12N5/0663 , A61K2035/124 , C12N5/0647 , C12N2500/35 , Y10T436/25375 , Y10T436/255
摘要： PROBLEM TO BE SOLVED: To provide methods for enriching a heterogenous mixture of bone marrow or blood constituents for stem cells by removal of non-stem cell constituents, including separation of the non-stem cell constituents using a tangential flow filtration device. SOLUTION: The cell populations enriched in stem cells and the like obtained by the use of the devices and methods can be used to prepare compositions suitable for infusion into individuals for the purpose of, for example, bone marrow reconstitution, or for the repair of injured tissue including cardiac muscle, and the like. COPYRIGHT: (C)2011,JPO&INPIT

10. 发明公开

KR20180022949A 향상되거나 증가된 항-종양 면역 반응을 유도하는 최적으로 활성화된 수지상 세포 审中-公开
标题翻译：增强或增加抗活化的树突最佳诱导肿瘤细胞的免疫应答
公开(公告)号：KR20180022949A
公开(公告)日：2018-03-06
申请号：KR20187002974
申请日：2016-06-29
申请人： NORTHWEST BIOTHERAPEUTICS INC
发明人： BOSCH MARNIX L
IPC分类号： C12N5/0784 , A61K35/15 , A61K39/00
CPC分类号： C12N5/064 , A61K35/15 , A61K39/00 , C12N2506/11
摘要： 본개시는암 및/또는종양을갖는개체에게투여하기위해사용될수 있는부분적으로성숙하고최적으로활성화된수지상세포를포함하는세포의집단을제공한다. 부분적으로성숙한수지상세포, 수지상세포성숙제와약 10 내지약 19시간동안접촉된세포들은투여시종양부위의영역에서종양항원을효율적으로흡수하여프로세싱하고, 성숙을완료하고, 후속적으로치료된개체의림프절로이동시킬수 있다. 일단림프절로이동되면, 완전히성숙한항원제시수지상세포는적절한사이토카인(예를들면, TNFα, IL-6, IL-8 및/또는 IL-12)을분비하고, 실질적이고최적인임상학적및/또는항-종양면역반응을유도하는 T 세포와접촉한다.
摘要翻译：本发明提供了一种细胞群，包括在部分成熟的树突细胞，其可用于给予患有癌症和/或肿瘤的受试者，并启用最好的。部分成熟的树突细胞，树突细胞小的分配和从约10至约19时所接触的细胞进行处理，以有效地吸收在给药后肿瘤，完全成熟的区域中的肿瘤抗原，和随后处理，而对象淋巴结中。一旦移动到淋巴结，完全成熟的抗原呈递树突状细胞是合适的细胞因子（例如，TNFα，IL-6，IL-8和/或IL-12）的分泌，和实际的和最佳的临床和/或所述诱导抗肿瘤免疫应答的T细胞。

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