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1.发明申请USE OF ANTI THIRD PARTY CENTRAL MEMORY T CELLS FOR ANTI-LEUKEMIA/LYMPHOMA TREATMENT 审中-公开使用抗第三方中央记忆T细胞进行抗白血病/淋巴瘤治疗
公开(公告)号：WO2012032526A2
公开(公告)日：2012-03-15
申请号：PCT/IL2011/000727
申请日：2011-09-08
申请人： YEDA RESEARCH AND DEVELOPMENT CO. LTD. , REISNER, Yair , LASK, Assaf , OPHIR, Eran , OR-GEVA, Noga , COHEN, Adva , AFIK, Ran , BACHAR-LUSTIG, Esther , EIDELSTEIN, Yaki
发明人： REISNER, Yair , LASK, Assaf , OPHIR, Eran , OR-GEVA, Noga , COHEN, Adva , AFIK, Ran , BACHAR-LUSTIG, Esther , EIDELSTEIN, Yaki
CPC分类号： A61K35/17 , A61K31/517 , A61K35/28 , A61K39/001 , A61K45/06 , A61K2035/124 , A61K2039/5158 , C12N5/0602 , C12N5/0636 , C12N5/0637 , C12N2501/2307 , C12N2501/2315 , C12N2501/2321 , A61K2300/00
摘要： A method of treating a disease in a subject in need thereof is disclosed. The method comprising: (a) transplanting a non-syngeneic cell or tissue graft to the subject; and (b) administering to the subject a therapeutically effective amount of an isolated population of cells comprising non-graft versus host (GVHD) inducing anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance-inducing cells and capable of homing to the lymph nodes following transplantation, and further wherein the cells are either: (i) non-syngeneic with both the subject and the graft; or (ii) non-syngeneic with the graft and syngeneic with the subject, thereby treating the subject.
摘要翻译： 公开了一种在有需要的受试者中治疗疾病的方法。 该方法包括：（a）将非同基因细胞或组织移植物移植到受试者; 和（b）向受试者施用治疗有效量的分离的细胞群，所述细胞群包含诱导具有中央记忆T淋巴细胞（Tcm）表型的抗第三方细胞的非移植物抗宿主细胞（GVHD），所述细胞是耐受性 - 诱导细胞并且能够在移植后归巢至淋巴结，并且进一步其中所述细胞是：（i）与受试者和移植物两者都不同基因; 或（ii）与移植物不同基因并与受试者同基因，从而治疗受试者。
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公开(公告)号：WO2022034593A1
公开(公告)日：2022-02-17
申请号：PCT/IL2021/050984
申请日：2021-08-11
发明人： REISNER, Yair , GLOBERSON LEVIN, Anat , BACHAR-LUSTIG, Esther , LASK, Assaf , NATHANSOHN-LEVI, Bar , WAKS, Tova , HORN, Galit , ESHHAR, Zelig
IPC分类号： C12N5/0783 , A61K35/17 , A61P35/00 , A61P35/04 , C07K14/725 , C07K16/28 , C12N5/00 , A61P35/02
摘要： A method of generating a population of genetically modified veto cells is disclosed. The method comprising: (a) providing a population of cells comprising T cells, the T cells comprising at least 40 % memory CD8+ T cells; (b) culturing the population of cells comprising T cells with an antigen or antigens under conditions which allow enrichment of tolerance-inducing antigen- specific cells having a central memory T-lymphocyte (Tcm) phenotype, the cells being depleted of graft versus host (GVH) reactivity; and (c) transducing the cells with a polynucleotide encoding a heterologous cell surface receptor comprising a T cell receptor signaling module, thereby generating the population of genetically modified veto cells.
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公开(公告)号：WO2018134824A1
公开(公告)日：2018-07-26
申请号：PCT/IL2018/050071
申请日：2018-01-18
IPC分类号： C12N5/0783 , A61K35/17 , C12N5/00 , A01K67/027
摘要： An isolated cytotoxic T-lymphocyte (CTL), said CTL being a tolerance inducing cell and substantially depleted of alloreactivity, and wherein said CTL does not comprise a central memory T- lymphocyte (Tcm) phenotype, the CTL being transduced to express a cell surface receptor comprising a T cell receptor signaling module, is disclosed. Methods of generating same and using same are also disclosed.
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公开(公告)号：WO2018002924A1
公开(公告)日：2018-01-04
申请号：PCT/IL2017/050716
申请日：2017-06-27
发明人： REISNER, Yair , OR-GEVA, Noga , GIDRON BUDOVSKY, Rotem , BACHAR-LUSTIG, Esther , LASK, Assaf , KAGAN, Sivan
IPC分类号： C12N5/0783 , A61K39/00 , A61K35/12 , A01K67/00
摘要： A method of generating an isolated population of non graft versus host disease (GvHD) inducing cells comprising a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance inducing cells and/or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) providing a population of at least 70 % memory T cells; (b) contacting the population of memory T cells with an antigen or antigens so as to allow enrichment of antigen reactive cells; and (c) culturing the cells resulting from step (b) in the presence of cytokines so as to allow proliferation of cells comprising the Tcm phenotype. Cells generated by the method, pharmaceutical compositions and methods of treatment are also disclosed.
摘要翻译： 产生包含中央记忆T淋巴细胞（Tcm）表型的分离的非移植物抗宿主病（GvHD）细胞群的方法，所述细胞为耐受诱导细胞和/或赋予抗 - 疾病活动，并且能够在移植后归巢至淋巴结。 该方法包括：（a）提供至少70％记忆T细胞的群体; （b）使记忆T细胞群体与一种或多种抗原接触以便富集抗原反应性细胞; 和（c）在存在细胞因子的情况下培养步骤（b）产生的细胞，以允许包含Tcm表型的细胞增殖。 还公开了由该方法产生的细胞，药物组合物和治疗方法。
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5.发明申请METHODS OF USING PULMONARY CELLS FOR TRANSPLANTATION AND INDUCTION OF TOLERANCE 审中-公开使用肺细胞移植和诱导耐受的方法
公开(公告)号：WO2017203520A1
公开(公告)日：2017-11-30
申请号：PCT/IL2017/050569
申请日：2017-05-22
摘要： A method of treating a pulmonary disorder or injury in a subject in need thereof is disclosed. The method comprising administering to the subject non-syngeneic pulmonary tissue cells in suspension comprising an effective amount of hematopoietic precursor cells (HPCs) or supplemented with HPCs, wherein the effective amount is a sufficient amount to achieve tolerance to the pulmonary tissue cells in the absence of chronic immunosuppressive regimen. A method of inducing donor specific tolerance in a subject in need of a pulmonary cell or tissue transplantation is also disclosed.
摘要翻译： 公开了一种治疗有需要的受试者的肺部病症或损伤的方法。 所述方法包括向所述对象施用包含有效量的造血前体细胞（HPC）或补充有HPC的悬浮液中的非同基因肺组织细胞，其中所述有效量足以在不存在的情况下实现对肺组织细胞的耐受性 慢性免疫抑制治疗方案。 还公开了在需要肺细胞或组织移植的受试者中诱导供体特异性耐受的方法。
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公开(公告)号：WO2013093920A2
公开(公告)日：2013-06-27
申请号：PCT/IL2012/050542
申请日：2012-12-20
IPC分类号： A61K35/18
CPC分类号： A61K35/28 , A61K31/198 , A61K31/255 , A61K31/661 , A61K31/675 , A61K31/7076 , A61K35/22 , A61K35/34 , A61K35/36 , A61K35/38 , A61K35/39 , A61K35/407 , A61K35/42 , A61K39/3955 , A61K2035/124 , A61K2039/507 , A61K2039/515 , C12N5/0087 , A61K2300/00
摘要： A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoietic cells, wherein the T cell depleted immature hematopoietic cells comprise less than 5 x 105 CD3+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5 x 106 CD34+ cells per kilogram body weight of the subject; and subsequently (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per kilogram body weight, thereby treating the subject.
摘要翻译： 公开了一种治疗需要非同基因细胞或组织移植物的受试者的方法。 所述方法包括：（a）向受试者移植剂量的T细胞耗尽的未成熟造血细胞，其中所述T细胞耗尽的未成熟造血细胞每个体重每公斤体重小于5×10 5个CD3 + T细胞，其中所述剂量 包括至少约5×10 6个CD34 +细胞/每公斤体重的受试者; 并且随后（b）向受试者施用治疗有效量的环磷酰胺，其中治疗有效量包含25-200mg /千克体重，从而治疗受试者。
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7.发明申请A COMBINATION THERAPY FOR A STABLE AND LONG TERM ENGRAFTMENT USING SPECIFIC PROTOCOLS FOR T/B CELL DEPLETION 审中-公开使用特定协议对T / B细胞去除的稳定和长期植入的组合治疗
公开(公告)号：WO2013093919A2
公开(公告)日：2013-06-27
申请号：PCT/IL2012/050541
申请日：2012-12-20
IPC分类号： A61K35/18
CPC分类号： A61K35/28 , A61K31/198 , A61K31/255 , A61K31/661 , A61K31/675 , A61K31/7076 , A61K35/22 , A61K35/34 , A61K35/36 , A61K35/38 , A61K35/39 , A61K35/407 , A61K35/42 , A61K39/3955 , A61K2035/124 , A61K2039/507 , A61K2039/515 , C12N5/0087 , A61K2300/00
摘要： A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoietic cells, wherein the T cell depleted immature hematopoietic cells comprise less than 5 x 105 CD3+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5 x 106 CD34+ cells per kilogram body weight of the subject, and wherein the T cell depleted immature hematopoietic cells are obtained by separating the T cells from the immature hematopoietic cells, by a method comprising: (i) adding an antibody to the immature hematopoietic cells that specifically binds to a surface marker, wherein the antibody is labeled with a magnetically responsive agent; (ii) immobilizing the immature hematopoietic cells specifically bound to the antibody labeled with the magnetically responsive agent in a matrix through a magnetic field; (iii) washing the matrix to remove unbound cells; and (iv) removing the magnetic field to elute bound cells from the matrix; and subsequently (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per kilogram body weight, thereby treating the subject.
摘要翻译： 公开了一种治疗需要非同基因细胞或组织移植物的受试者的方法。 所述方法包括：（a）向受试者移植剂量的T细胞耗尽的未成熟造血细胞，其中所述T细胞耗尽的未成熟造血细胞每个体重每公斤体重小于5×10 5个CD3 + T细胞，其中所述剂量 包括至少约5×10 6个CD34 +细胞/千克体重的受试者，并且其中所述T细胞耗尽的未成熟造血细胞是通过从未成熟的造血细胞中分离T细胞获得的，方法包括：（i） 涉及特异性结合表面标志物的未成熟造血细胞，其中所述抗体用磁性响应剂标记; （ii）通过磁场将特异性结合于用磁响应剂标记的抗体的未成熟造血细胞固定在基质中; （iii）洗涤基质以除去未结合的细胞; 和（iv）去除磁场以从基质中洗脱结合的细胞; 并且随后（b）向受试者施用治疗有效量的环磷酰胺，其中治疗有效量包含25-200mg /千克体重，从而治疗受试者。
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公开(公告)号：WO2021024264A2
公开(公告)日：2021-02-11
申请号：PCT/IL2020/050865
申请日：2020-08-06
发明人： REISNER, Yair , BACHAR-LUSTIG, Esther , LASK, Assaf , OR-GEVA, Noga , GIDRON BUDOVSKY, Rotem , SIDLIK MUSKATEL, Rakefet
摘要： Methods of generating an isolated population of non-graft versus host disease (GVHD) inducing cells comprising a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance inducing cells and/or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation, are disclosed. Cells generated by the methods, pharmaceutical compositions and methods of treatment are also disclosed.
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9.发明申请ANTI THIRD PARTY CENTRAL MEMORY T CELLS, METHODS OF PRODUCING SAME AND USE OF SAME IN TRANSPLANTATION AND DISEASE TREATMENT 审中-公开第三方中央记忆体细胞，其生产方法及其在移植和疾病治疗中的应用
公开(公告)号：WO2013035099A1
公开(公告)日：2013-03-14
申请号：PCT/IL2012/050354
申请日：2012-09-06
申请人： YEDA RESEARCH AND DEVELOPMENT CO. LTD. , REISNER, Yair , EIDELSTEIN, Yaki , OPHIR, Eran , LASK, Assaf , AFIK, Ran , OR-GEVA, Noga , BACHAR-LUSTIG, Esther
发明人： REISNER, Yair , EIDELSTEIN, Yaki , OPHIR, Eran , LASK, Assaf , AFIK, Ran , OR-GEVA, Noga , BACHAR-LUSTIG, Esther
IPC分类号： A61K39/00
CPC分类号： A61K35/17 , A61K35/22 , A61K35/26 , A61K35/28 , A61K35/34 , A61K35/36 , A61K35/38 , A61K35/39 , A61K35/407 , A61K35/42 , A61K39/001 , A61K2035/122 , A61K2035/124 , A61K2039/5158 , C12N5/0636 , C12N5/0637 , C12N2501/2307 , C12N2501/2315 , C12N2501/2321 , C12N2502/1121
摘要： A method of generating an isolated population of cells comprising anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance-inducing cells and/or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) contacting peripheral blood mononuclear cells (PBMC) with a third party antigen or antigens in the presence of IL-21 so as to allow enrichment of antigen reactive cells; and (b) culturing the cells resulting from step (a) in the presence of IL- 21, IL-15 and IL-7 in an antigen free environment so as to allow proliferation of cells comprising the central memory T-lymphocyte (Tcm) phenotype.
摘要翻译： 一种产生分离的细胞群的方法，包括具有中枢记忆T淋巴细胞（Tcm）表型的抗第三方细胞，所述细胞是耐受诱导细胞和/或具有抗病活性，并能够归巢于 公布了移植后的淋巴结。 该方法包括：（a）在IL-21存在下使外周血单核细胞（PBMC）与第三方抗原或抗原接触，以便使抗原反应性细胞富集; 和（b）在抗原自由环境中在IL-21，IL-15和IL-7存在下培养由步骤（a）产生的细胞，以使得包含中央记忆T淋巴细胞（Tcm）的细胞增殖， 表型。
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公开(公告)号：WO2012032525A3
公开(公告)日：2012-03-15
申请号：PCT/IL2011/000726
申请日：2011-09-08
申请人： YEDA RESEARCH AND DEVELOPMENT CO. LTD. , REISNER, Yair , BACHAR-LUSTIG, Esther , TCHORSH-YUTSIS, Dalit
IPC分类号： C07K16/28
摘要： A method of treating a subject in need of a cell or tissue transplant is disclosed. The method comprising (a) transplanting a non-syngeneic cell or tissue transplant into the subject, wherein the transplant comprises bone marrow or lymphoid cells; and (b) administering to the subject a therapeutically effective amount of an immunosuppressive regimen comprising a Sphingosine 1-Phosphate Receptor Agonist, a B7 molecule inhibitor and a CD2/CD58 pathway inhibitor, thereby treating the subject.
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