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    Monocyte derived cells with immunostimulating properties, their preparation and uses
    3.
    发明授权
    Monocyte derived cells with immunostimulating properties, their preparation and uses 失效
    单核细胞衍生细胞具有免疫刺激性质，其制备和用途

    公开(公告)号：US06399372B1

    公开(公告)日：2002-06-04

    申请号：US09647534

    申请日：2000-10-02

    申请人： Jacques Bartholeyns ,  Mohamed Chokri ,  Nathalie Latour

    发明人： Jacques Bartholeyns ,  Mohamed Chokri ,  Nathalie Latour

    IPC分类号： C12N500

    CPC分类号： C12N5/0645 ,  A61K38/00 ,  A61K2035/124 ,  C12N2510/00

    摘要： The invention relates to stimulated monocyte derived cells presenting the following characteristics: 1) increased release, with respect to normal monocyte derived cells, of for instance PDGF (platelet derived growth factor), and increased presence, on their membranes, with respect to normal monocyte derived cells, of for instance CD1&agr;, and/or: 2) presence in their nucleus of at least one exogenous nucleic acid which has been integrated in the absence of the monocyte derived cell division. These stimulated monocyte derived cells can be the active substance of pharmaceutical compositions.

    摘要翻译： 本发明涉及具有以下特征的受刺激的单核细胞衍生细胞：1）相对于正常单核细胞来源的细胞，例如PDGF（血小板衍生生长因子）的释放增加，并且在其膜上相对于正常单核细胞增加的存在 衍生的细胞，例如CD1α，和/或：2）在其核中存在已经在不存在单核细胞衍生的细胞分裂的情况下整合的至少一种外源核酸。 这些刺激的单核细胞来源的细胞可以是药物组合物的活性物质。

    Macrophages, process for preparing the same and their use as active substances of pharmaceutical compositions
    4.
    发明授权
    Macrophages, process for preparing the same and their use as active substances of pharmaceutical compositions 失效
    巨噬细胞，其制备方法及其作为药物组合物的活性物质的用途

    公开(公告)号：US6051432A

    公开(公告)日：2000-04-18

    申请号：US400875

    申请日：1999-09-22

    申请人： Mohamed Chokri ,  Jacques Bartholeyns

    发明人： Mohamed Chokri ,  Jacques Bartholeyns

    IPC分类号： A61K35/12 ,  C12N5/0786 ,  C12Q1/00 ,  G01N33/53

    CPC分类号： C12N5/0645 ,  A61K2035/124 ,  C12N2500/38 ,  C12N2501/22 ,  C12N2501/24 ,  Y10S435/81

    摘要： The invention relates to macrophages which have at least one of the following properties: their cytotoxic activity without IFN-.gamma. is increased by about 20 to 30% with respect to standard macrophages, and is preferably of about 70%; their cytotoxic activity with IFN-.gamma. is increased by about 20 to about 40% with respect to standard macrophages, and is preferably of about 93%; the extension of the deactivation of the cytotoxic activity in reply to an activation of IFN-.gamma. is in a ratio such that after 60 h of activation with IFN-.gamma., the cytotoxic activity is higher than or equal to 30%, preferably of about 55%, compared to the maximum cytotoxic activity presented by the macrophages due to IFN-.gamma. activation, with said cytotoxic activity being measured as the percentage of inhibition of 3-H thymidine incorporation by target tumoral cells, particularly U 937 cells.

    摘要翻译： 本发明涉及具有以下性质中的至少一种的巨噬细胞：其相对于标准巨噬细胞而言，其IFN-γ的细胞毒性活性增加约20％至30％，优选为约70％; 其与IFN-γ的细胞毒活性相对于标准巨噬细胞增加约20至约40％，优选为约93％; 与IFN-γ的激活相应的细胞毒活性的失活的延长使得在用IFN-γ活化60小时后，细胞毒活性高于或等于30％，优选约55 与由IFN-γ激活引起的巨噬细胞呈现的最大细胞毒活性相比，所述细胞毒活性被测量为目标肿瘤细胞尤其是U937细胞3-H胸苷掺入的抑制百分比。

    Macrophages, process for preparing the same and their use as active substances of pharmaceutical compositions
    5.
    发明授权
    Macrophages, process for preparing the same and their use as active substances of pharmaceutical compositions 失效
    巨噬细胞，其制备方法及其作为药物组合物的活性物质的用途

    公开(公告)号：US5662899A

    公开(公告)日：1997-09-02

    申请号：US374629

    申请日：1995-01-17

    申请人： Mohamed Chokri ,  Jacques Bartholeyns

    发明人： Mohamed Chokri ,  Jacques Bartholeyns

    IPC分类号： A61K35/12 ,  A61K35/15 ,  A61K35/17 ,  A61P35/00 ,  C07K16/46 ,  C12N5/0786 ,  C12P21/08 ,  C12N5/08 ,  A61K35/14 ,  A61K35/26 ,  A61K35/28

    CPC分类号： A61K35/17 ,  A61K35/15 ,  C07K16/468 ,  C12N5/0645 ,  A61K2035/124 ,  C12N2500/38 ,  C12N2501/02 ,  C12N2501/22 ,  C12N2501/24

    摘要： Macrophages have been developed, which possess at least one of the following properties:their cytotoxic activity without IFN-.gamma. is increased by about 20 to 30% with respect to standard macrophages, and is preferably of about 70%;their cytotoxic activity with IFN-.gamma. is increased by about 20 to about 40% with respect to standard macrophages, and is preferably of about 93%;deactivation of the cytotoxic activity following activation of IFN-.gamma. is such that sixty hours after activation with IFN-.gamma., the residual cytotoxic activity is at least 30%, preferably about 55%, of the maximum cytotoxic activity presented by the macrophages due to IFN-.gamma. activation, with said cytotoxic activity being measured as a percentage of the inhibition of 3-H thymidine incorporation by target tumoral cells, particularly U 937 cells. The macrophages are prepared by culturing healthy human monocytes and lymphocytes in a culture medium containing 1,25-dihydroxy vitamin D.sub.3 and GM-CSF.

    摘要翻译： PCT No.PCT / EP93 / 01232 Sec。 371日期1995年1月17日 102（e）日期1995年1月17日PCT提交1993年5月18日PCT公布。 第WO94 / 26875号公报 日期1994年11月24日已经开发了具有至少以下性质之一的巨噬细胞：相对于标准巨噬细胞，其IFN-γ的细胞毒性活性增加约20至30％，优选为约70％; 其与IFN-γ的细胞毒活性相对于标准巨噬细胞增加约20至约40％，优选为约93％; IFN-γ活化后细胞毒活性的失活使得用IFN-γ活化后的六十小时，剩余的细胞毒性活性是巨噬细胞由于IFN引起的最大细胞毒性活性的至少30％，优选约55％ - γ激活，所述细胞毒活性被测量为目标肿瘤细胞，特别是U 937细胞的3-H胸苷掺入的抑制百分比。 通过在含有1,25-二羟基维生素D3和GM-CSF的培养基中培养健康的人单核细胞和淋巴细胞来制备巨噬细胞。

    Macrophages, process for preparing the same and their use as active substances of pharmaceutical compositions
    6.
    发明授权
    Macrophages, process for preparing the same and their use as active substances of pharmaceutical compositions 失效
    巨噬细胞，其制备方法及其作为药物组合物的活性物质的用途

    公开(公告)号：US06821516B1

    公开(公告)日：2004-11-23

    申请号：US09304564

    申请日：1999-05-04

    申请人： Mohamed Chokri ,  Jacques Bartholeyns

    发明人： Mohamed Chokri ,  Jacques Bartholeyns

    IPC分类号： A61K39395

    CPC分类号： C12N5/0645 ,  A61K2035/124 ,  C12N2500/38 ,  C12N2501/22 ,  C12N2501/24 ,  Y10S435/81

    摘要： The invention relates to macrophages which have at least one of the following properties: their cytotoxic activity without IFN-&ggr; is increased by about 20 to 30% with respect to standard macrophages, and is preferably of about 70%; their cytotoxic activity with IFN-&ggr; is increased by about 20 to about 40% with respect to standard macrophages, and is preferably of about 93%; the extension of the deactivation of the cytotoxic activity in reply to an activation of IFN-&ggr; is in a ratio such that after 60h of activation with IFN-&ggr;, the cytotoxic activity is higher than or equal to 30%, preferably of about 55%, compared to the maximum cytotoxic activity presented by the macrophages due to IFN-&ggr; activation, with said cytotoxic activity being measured as the percentage of inhibition of 3-H thymidine incorporation by target tumoral cells, particularly U 937 cells.

    摘要翻译： 本发明涉及具有以下性质中的至少一种的巨噬细胞：相对于标准巨噬细胞，其IFN-γ的细胞毒活性增加约20至30％，优选为约70％; 其与IFN-γ的细胞毒活性相对于标准巨噬细胞增加约20至约40％，优选为约93％; 与IFN-γ的激活相应的细胞毒活性的失活的延长是使得在用IFN-γ活化60小时后，细胞毒活性高于或等于30％，优选约55％ ，与由IFN-γ活化引起的巨噬细胞呈现的最大细胞毒活性相比，所述细胞毒活性被测量为目标肿瘤细胞，特别是U 937细胞的3-H胸苷掺入的抑制百分比。

    Apoptotic bodies, monocyte derived cells containing the same, a process for their preparation and their uses as vaccines
    9.
    发明授权
    Apoptotic bodies, monocyte derived cells containing the same, a process for their preparation and their uses as vaccines 失效
    凋亡体，含有其的单核细胞衍生细胞，其制备方法及其作为疫苗的用途

    公开(公告)号：US06703016B1

    公开(公告)日：2004-03-09

    申请号：US09700108

    申请日：2000-12-28

    申请人： Marc Gregoire ,  Jacques Bartholeyns

    发明人： Marc Gregoire ,  Jacques Bartholeyns

    IPC分类号： A61K4800

    CPC分类号： A61K39/0011 ,  A61K38/00 ,  A61K2039/5154 ,  C12N2500/36

    摘要： The present invention relates to apoptotic bodies derived from human tumor cells or cell lines recovered from patient's tumor biopsy and induced to apoptotis, said apoptotic bodies having the following characteristics: they maintain plasma membrane integrity, they are vesicles above about 0,1 &mgr;m, they contain intact mitochondria and cleaved nuclear DNA originating from the tumor cells, they present unmasked tumor antigens on their membranes, they present specific tumor and MHC antigens from the patient. The invention also provides new monocytes derived cells, which can be used as anti-tumor vaccines after integration of apoptotic bodies. Apoptotic bodies are phagocytosed and processed by monocyte derived antigen presenting cells and potentiate the effective tumor antigenic presentation to the immune system.

    摘要翻译： 本发明涉及源自人肿瘤细胞或从患者肿瘤活组织检查中诱导凋亡的细胞系的凋亡小体，所述凋亡小体具有以下特征：它们保持质膜完整性，它们是高于约0.1μm的囊泡，它们 含有源自肿瘤细胞的完整的线粒体和切割的核DNA，它们在其膜上存在未被掩蔽的肿瘤抗原，它们呈现来自患者的特异性肿瘤和MHC抗原。 本发明还提供新的单核细胞衍生细胞，其可以在凋亡小体整合后用作抗肿瘤疫苗。 细胞凋亡体被吞噬细胞并由单核细胞衍生的抗原呈递细胞处理，并增强免疫系统的有效肿瘤抗原呈递。

    Macrophages, process for preparing the same and their use as active substances of pharmaceutical compositions
    10.
    发明授权
    Macrophages, process for preparing the same and their use as active substances of pharmaceutical compositions 失效
    巨噬细胞，其制备方法及其作为药物组合物的活性物质的用途

    公开(公告)号：US06540994B1

    公开(公告)日：2003-04-01

    申请号：US09304563

    申请日：1999-05-04

    申请人： Mohamed Chokri ,  Jacques Bartholeyns

    发明人： Mohamed Chokri ,  Jacques Bartholeyns

    IPC分类号： A61K4800

    CPC分类号： C12N5/0645 ,  A61K2035/124 ,  C12N2500/38 ,  C12N2501/22 ,  C12N2501/24 ,  Y10S435/81

    摘要： The invention relates to macrophages which have at least one of the following properties: their cytotoxic activity without IFN-7 is increased by about 20 to 30% with respect to standard macrophages, and is preferably of about 70%; their cytotoxic activity with IFN-&ggr; is increased by about 20 to about 40% with respect to standard macrophages, and is preferably of about 93%; the extension of the deactivation of the cytotoxic activity in reply to an activation of IFN-&ggr; is in a ratio such that after 60h of activation with IFN-&ggr;, the cytotoxic activity is higher than or equal to 30%, preferably of about 55%, compared to the maximum cytotoxic activity presented by the macrophages due to IFN-&ggr; activation, with said cytotoxic activity being measured as the percentage of inhibition of 3-H thymidine incorporation by target tumoral cells, particularly U 937 cells.

    摘要翻译： 本发明涉及具有以下性质中的至少一个的巨噬细胞：其相对于标准巨噬细胞而言，其无IFN-7的细胞毒活性增加约20至30％，优选为约70％; 其与IFN-γ的细胞毒活性相对于标准巨噬细胞增加约20至约40％，优选为约93％; 与IFN-γ的激活相应的细胞毒活性的失活的延长是使得在用IFN-γ活化60小时后，细胞毒活性高于或等于30％，优选约55％ ，与由IFN-γ活化引起的巨噬细胞呈现的最大细胞毒活性相比，所述细胞毒活性被测量为目标肿瘤细胞，特别是U 937细胞的3-H胸苷掺入的抑制百分比。