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1. 发明申请

WO1995032729A1 SHORT-TERM ANTI-CD3 STIMULATION OF LYMPHOCYTES TO INCREASE THEIR IN VIVO ACTIVITY 审中-公开
标题翻译：慢性抗CD3刺激淋巴细胞增加体内活性
公开(公告)号：WO1995032729A1
公开(公告)日：1995-12-07
申请号：PCT/US1995006703
申请日：1995-05-31
申请人： OCHOA, Augusto, Carlos , SAXTON, Mark, L. , LONGO, Dan, L.
IPC分类号： A61K38/21
CPC分类号： C12N5/0648 , A61K38/2013 , A61K39/395 , A61K2035/124 , A61K2039/5158 , C12N5/0636 , A61K2300/00
摘要： A tumor-bearing mammal is treated by stimulating lymphocytes, including T lymphocyte subsets, in vitro in the presence of an antibody to a lymphocyte surface receptor for less than about 24 hours, optionally in the presence of IL-2, to form stimulated lymphocytes; infusing the stimulated lymphocytes into the tumor-bearing mammal; and administering one or more lymphokines to the mammal. The stimulated lymphocytes display enhanced immunotherapeutic activity, including increased cytotoxicity or lymphokine production in vivo, resulting in a decrease in the tumor burden by at least about 20 %.
摘要翻译：在淋巴细胞表面受体抗体存在下，任选地在IL-2存在下，通过刺激淋巴细胞（包括T淋巴细胞亚群）来治疗肿瘤的哺乳动物，以形成刺激的淋巴细胞; 将刺激的淋巴细胞注入荷瘤哺乳动物; 以及向哺乳动物施用一种或多种淋巴因子。刺激的淋巴细胞表现出增强的免疫治疗活性，包括体内增加的细胞毒性或淋巴因子产生，导致肿瘤负荷降低至少约20％。

2. 发明申请

WO2008073858A3 CANCER CHEMOPREVENTION STRATEGY BASED ON LOSS OF IMPRINTING OF IGF2 审中-公开
公开(公告)号：WO2008073858A3
公开(公告)日：2008-06-19
申请号：PCT/US2007/086889
申请日：2007-12-07
申请人： THE JOHNS HOPKINS UNIVERSITY , NATIONAL INSTITUTES OF HEALTH , FEINBERG, Andrew, P. , LEVCHENKO, Andre , LONGO, Dan, L. , KO, Minoru, S.H.
发明人： FEINBERG, Andrew, P. , LEVCHENKO, Andre , LONGO, Dan, L. , KO, Minoru, S.H.
IPC分类号： A61K31/00
摘要： The present invention relates to targets of loss of imprinting (LOI) affected IGF2 gene products in pre-malignant tissues, where methods of inhibiting those targets, including IGFRl, are disclosed to prevent tumor development in subjects at risk for developing colorectal cancer (CRC). The present invention also relates to methods of identifying increased risk in developing CRC in a subject, including methods of assessing the efficacy of a chemotherapeutic regimen. Further, the present invention relates to methods for identifying anti-neoplastic agents.

3. 发明申请

WO2005118878A3 METHODS OF SCREENING FOR CELL PROLIFERATION OR NEOPLASTIC DISORDERS 审中-公开
标题翻译：筛选细胞增殖或神经障碍的方法
公开(公告)号：WO2005118878A3
公开(公告)日：2007-11-15
申请号：PCT/US2005019735
申请日：2005-06-03
申请人： UNIV JOHNS HOPKINS , NAT INST HEALTH , FEINBERG ANDREW P , IACOBUZIO-DONAHUE CHRISTINE A , LONGO DAN L , KO MINORU
发明人： FEINBERG ANDREW P , IACOBUZIO-DONAHUE CHRISTINE A , LONGO DAN L , KO MINORU
IPC分类号： A61K39/395 , C07K16/00 , C12Q1/68 , G01N33/50 , G01N33/53 , G01N33/574
CPC分类号： G01N33/574 , C12Q1/6886 , C12Q2600/154 , C12Q2600/156 , G01N33/5017 , G01N33/5023 , G01N33/57419 , G01N33/57434
摘要： The invention relates to methods and compositions for identifying subjects having, or predisposed to having, a neoplastic or cell proliferation or neoplastic disorder. The methods are applicable to any type of tissue sample and can be conducted on otherwise normal tissue.
摘要翻译：本发明涉及用于鉴定具有或倾向于具有肿瘤或细胞增殖或肿瘤性疾病的受试者的方法和组合物。该方法适用于任何类型的组织样品，并且可以在其他正常组织上进行。

4. 发明申请

WO1995025528A1 METHOD OF ENHANCING THE IMMUNOTHERAPEUTIC ACTIVITY OF IMMUNE CELLS BY DEPLETION/POSITIVE SELECTION 审中-公开
标题翻译：通过去除/积极选择增强免疫细胞免疫活性的方法
公开(公告)号：WO1995025528A1
公开(公告)日：1995-09-28
申请号：PCT/US1995002974
申请日：1995-03-14
申请人： OCHOA, Augusto, Carlos , SAXTON, Mark, L. , LONGO, Dan, L.
IPC分类号： A61K35/00
CPC分类号： C12N5/0636 , A61K9/127 , A61K31/675 , A61K35/17 , A61K35/26 , A61K38/2013 , A61K2039/5158 , C07K16/2809 , C12N5/0087 , C12N2501/125 , C12N2501/23 , C12N2501/515 , A61K2300/00
摘要： The present invention provides a method for enhancing the immunotherapeutic activity, e.g., antitumor activity, of immune cells by depleting immune cells of a cell subset that down-regulates the immune response, such as either CD4 or CD8 lymphocytes. The remaining depleted immune cell population or the separated immune cell subsets then are cultured in the presence of an antibody to a lymphocyte surface receptor, preferably an anti-CD3 monoclonal antibody (MoAb), optionally in the presence of a relatively minor amount of interleukin-2 (IL-2). These stimulated cells then are optionally additionally cultured in the presence of IL-2 without an antibody to a lymphocyte surface receptor. The present invention also provides a method of treating a mammal having tumors or immunizing a mammal against tumors by administering the stimulated depleted immune cell population or a stimulated immune cell subset to a mammal, advantageously together with an immunosuppressant, and with liposomal IL-2. The invention further provides a method of transferring the immunity of mammals that are treated or immunized in accordance with the invention by extracting splenocytes from these mammals and administering these splenocytes to a second mammal.
摘要翻译：本发明提供了通过消耗下调免疫应答的细胞亚群（例如CD4 +或CD8 +淋巴细胞）的免疫细胞来增强免疫细胞的免疫治疗活性（例如抗肿瘤活性）的方法。然后，在抗体对淋巴细胞表面受体（优选抗CD3单克隆抗体（MoAb））的存在下，任选地在相对少量的白细胞介素-1的存在下培养剩余的耗尽的免疫细胞群体或分离的免疫细胞亚群。 2（IL-2）。然后任选地在IL-2存在下额外培养这些刺激的细胞，而不需要针对淋巴细胞表面受体的抗体。本发明还提供了一种治疗具有肿瘤的哺乳动物或免疫哺乳动物免受肿瘤的方法，所述哺乳动物有利地与免疫抑制剂一起向哺乳动物施用刺激的耗尽的免疫细胞群或刺激的免疫细胞亚群，以及与脂质体IL-2。本发明还提供了通过从这些哺乳动物中提取脾细胞并将这些脾细胞施用于第二哺乳动物来转移根据本发明治疗或免疫的哺乳动物的免疫力的方法。

5. 发明申请

WO2008073858A9 CANCER CHEMOPREVENTION STRATEGY BASED ON LOSS OF IMPRINTING OF IGF2 审中-公开
标题翻译：基于IGF2缺失的癌症化疗策略
公开(公告)号：WO2008073858A9
公开(公告)日：2008-12-04
申请号：PCT/US2007086889
申请日：2007-12-07
申请人： UNIV JOHNS HOPKINS , NAT INST HEALTH , FEINBERG ANDREW P , LEVCHENKO ANDRE , LONGO DAN L , KO MINORU S H
发明人： FEINBERG ANDREW P , LEVCHENKO ANDRE , LONGO DAN L , KO MINORU S H
IPC分类号： A61K31/00
CPC分类号： A61K31/704 , A61K31/00 , C12Q1/6886 , C12Q2600/106 , C12Q2600/136 , C12Q2600/158
摘要： The present invention relates to targets of loss of imprinting (LOI) affected IGF2 gene products in pre-malignant tissues, where methods of inhibiting those targets, including IGFRl, are disclosed to prevent tumor development in subjects at risk for developing colorectal cancer (CRC). The present invention also relates to methods of identifying increased risk in developing CRC in a subject, including methods of assessing the efficacy of a chemotherapeutic regimen. Further, the present invention relates to methods for identifying anti-neoplastic agents.
摘要翻译：本发明涉及在恶性恶性组织中影响IGF2基因产物的印记损失（LOI）靶标，其中公开了抑制这些靶标的方法，包括IGFR1，以预防发展为结肠直肠癌（CRC）的风险的受试者的肿瘤发展。。本发明还涉及确定在受试者中发展CRC的增加的风险的方法，包括评估化疗方案的功效的方法。此外，本发明涉及用于鉴定抗肿瘤剂的方法。

6. 发明申请

WO2008073858A2 CANCER CHEMOPREVENTION STRATEGY BASED ON LOSS OF IMPRINTING OF IGF2 审中-公开
标题翻译：基于IGF2印迹缺失的化疗预防策略
公开(公告)号：WO2008073858A2
公开(公告)日：2008-06-19
申请号：PCT/US2007086889
申请日：2007-12-07
申请人： UNIV JOHNS HOPKINS , NAT INST HEALTH , FEINBERG ANDREW P , LEVCHENKO ANDRE , LONGO DAN L , KO MINORU S H
发明人： FEINBERG ANDREW P , LEVCHENKO ANDRE , LONGO DAN L , KO MINORU S H
IPC分类号： A61K39/395 , A61K31/704
CPC分类号： A61K31/704 , A61K31/00 , C12Q1/6886 , C12Q2600/106 , C12Q2600/136 , C12Q2600/158
摘要： The present invention relates to targets of loss of imprinting (LOI) affected IGF2 gene products in pre-malignant tissues, where methods of inhibiting those targets, including IGFRl, are disclosed to prevent tumor development in subjects at risk for developing colorectal cancer (CRC). The present invention also relates to methods of identifying increased risk in developing CRC in a subject, including methods of assessing the efficacy of a chemotherapeutic regimen. Further, the present invention relates to methods for identifying anti-neoplastic agents.
摘要翻译：本发明涉及在恶变前组织中损伤印迹（LOI）受影响的IGF2基因产物的靶标，其中公开了抑制这些靶标（包括IGFR1）的方法以防止处于发展结肠直肠癌（CRC）风险的受试者中的肿瘤发展，。本发明还涉及鉴定受试者中发展为CRC的风险增加的方法，包括评估化学疗法方案功效的方法。此外，本发明涉及鉴定抗肿瘤剂的方法。

7. 发明申请

WO1993000918A1 SHORT-TERM ANTI-CD3 STIMULATION OF LYMPHOCYTES TO INCREASE THEIR IN VIVO ACTIVITY 审中-公开
标题翻译：慢性抗CD3刺激淋巴细胞增加体内活性
公开(公告)号：WO1993000918A1
公开(公告)日：1993-01-21
申请号：PCT/US1992005673
申请日：1992-07-10
申请人： OCHOA, Augusto, C. , LOEFFLER, Cynthia , URBA, Walter , LONGO, Dan, L.
IPC分类号： A61K37/00
CPC分类号： C12N5/0636 , A61K38/2013 , A61K2035/124 , C12N2501/23 , C12N2501/515 , A61K38/20 , A61K35/14 , A61K2300/00
摘要： The present invention is directed to a method of increasing the in vivo immune response of lymphocytes by stimulating the lymphocytes in vitro in the presence of an anti-CD3 monoclonal antibody for less than about 24 hours to form stimulated lymphocytes; infusing the stimulated lymphocytes into a tumor-bearing mammal; and administering IL-2 to the mammal. As a result of this method, the anti-CD3 stimulated lymphocytes display enhanced immunotherapeutic, e.g., cytotoxicity or lymphokine production, in vivo as represented by a decrease in the number of tumors by at least about 20 %.
摘要翻译：本发明涉及通过在抗CD3单克隆抗体的存在下体外刺激淋巴细胞少于约24小时来增加淋巴细胞的体内免疫应答以形成刺激的淋巴细胞的方法; 将刺激的淋巴细胞注入荷瘤哺乳动物; 并向哺乳动物施用IL-2。作为该方法的结果，抗CD3刺激的淋巴细胞在体内显示增强的免疫治疗，例如细胞毒性或淋巴因子生成，如肿瘤数量的减少至少约20％所示。

8. 发明申请

WO2005118878A2 METHODS OF SCREENING FOR CELL PROLIFERATION OR NEOPLASTIC DISORDERS 审中-公开
标题翻译：筛选细胞增殖或神经障碍的方法
公开(公告)号：WO2005118878A2
公开(公告)日：2005-12-15
申请号：PCT/US2005/019735
申请日：2005-06-03
申请人： THE JOHNS HOPKINS UNIVERSITY , NATIONAL INSTITUTE OF HEALTH , FEINBERG, Andrew, P. , IACOBUZIO-DONAHUE, Christine, A. , LONGO, Dan, L. , KO, Minoru
发明人： FEINBERG, Andrew, P. , IACOBUZIO-DONAHUE, Christine, A. , LONGO, Dan, L. , KO, Minoru
IPC分类号： C12Q1/68
CPC分类号： G01N33/574 , C12Q1/6886 , C12Q2600/154 , C12Q2600/156 , G01N33/5017 , G01N33/5023 , G01N33/57419 , G01N33/57434
摘要： The invention relates to methods and compositions for identifying subjects having, or predisposed to having, a neoplastic or cell proliferation or neoplastic disorder. The methods are applicable to any type of tissue sample and can be conducted on otherwise normal tissue.
摘要翻译：本发明涉及用于鉴定具有或倾向于具有肿瘤或细胞增殖或肿瘤性疾病的受试者的方法和组合物。该方法适用于任何类型的组织样品，并且可以在其他正常组织上进行。

9. 发明申请

WO1993019605A1 EVALUATION AND TREATMENT OF PATIENTS WITH PROGRESSIVE IMMUNOSUPPRESSION 审中-公开
标题翻译：具有渐进性免疫抑制作用的患者的评估和治疗
公开(公告)号：WO1993019605A1
公开(公告)日：1993-10-14
申请号：PCT/US1993002936
申请日：1993-04-06
申请人： OCHOA, Augusto, C. , MIZOGUCHI, Hiromoto , O'SHEA, John, J. , LONGO, Dan, L. , LOEFFLER, Cynthia, M. , GHOSH, Paritosh , YOUNG , Howard, A.
IPC分类号： A01N63/00
CPC分类号： C07K16/18 , A61K38/2013 , A61K39/00 , C07K14/4702 , C07K14/4703 , A61K2300/00
摘要： A soluble immunosuppressive factor present in serum derived from tumor-bearing mammals, is associated with changes in TCR protein subunit levels, T lymphocyte signal transduction pathway proteins. These changes provide a method of determining the level of immunosuppression in a mammal by determining the level of expression of at least one selected TCR subunit protein, a protein in the T lymphocyte signal transduction pathway, or of the NF- kappa B/rel family and comparing the level and pattern to that found in non-immunosuppressed individuals. The method is useful to identify patients having T lymphocytes capable of activation for immunotherapy and for identifying agents which cause or reverse immunosuppression. An isolated immunosuppressive factor associated with the level of expression of the proteins is useful for suppressing the immune response, for example, in organ transplantation.
摘要翻译：存在于源自荷瘤哺乳动物的血清中的可溶性免疫抑制因子与TCR蛋白亚基水平，T淋巴细胞信号转导途径蛋白质的变化相关。这些变化提供了通过确定至少一种选择的TCR亚基蛋白，T淋巴细胞信号转导途径中的蛋白质或NF-κB/ rel家族的表达水平来确定哺乳动物免疫抑制水平的方法，以及将水平和模式与非免疫抑制个体的水平和模式进行比较。该方法可用于鉴定具有能够激活免疫治疗的T淋巴细胞的患者和用于鉴定引起或逆转免疫抑制的药物。与蛋白质表达水平相关的分离的免疫抑制因子可用于抑制免疫应答，例如在器官移植中。

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