Methods for use of TSLP and agonists and antagonists thereof
    1.
    发明申请
    Methods for use of TSLP and agonists and antagonists thereof 审中-公开
    使用TSLP及其激动剂及其拮抗剂的方法

    公开(公告)号:US20050249712A1

    公开(公告)日:2005-11-10

    申请号:US11084408

    申请日:2005-03-18

    摘要: Methods are disclosed herein for specifically inducing proliferation of CD4+ T cells. The methods are of use in treating immunodeficiencies, such as an immunodeficiency produced by infection with an immunodeficiency virus, such as infection with a human immunodeficiency virus (HIV). The methods include contacting isolated mammalian CD4+ T cells with an effective amount of a thymic stromal derived lymphopoietin (TSLP) polypeptide or a therapeutically effective amount of nucleic acid encoding the TSLP polypeptide, thereby inducing proliferation of the T cells. Methods are also disclosed for treating an IgE mediated disorder, such as asthma. The methods include administering to a subject a therapeutically effective amount of a TSLP antagonist. Transgenic mice are also disclosed herein. The somatic and germ cells of these mice include a disrupted thymic stromal lymphopoietin receptor (TSLP) gene, the disruption being sufficient to inhibit the interaction of TSLP with its receptor, and a disrupted γc gene, the disruption being sufficient to reduce signaling through the γc. The mice exhibit diminished thymic cellularity. Methods of using these mice for drug screening are also disclosed.

    摘要翻译: 本文公开了用于特异性诱导CD4 + T细胞增殖的方法。 该方法可用于治疗免疫缺陷,例如由免疫缺陷病毒感染产生的免疫缺陷,例如人免疫缺陷病毒(HIV)的感染。 所述方法包括使分离的哺乳动物CD4 + T细胞与有效量的胸腺基质衍生的淋巴细胞生成素(TSLP)多肽或治疗有效量的编码TSLP多肽的核酸接触,从而诱导T细胞的增殖。 还公开了用于治疗IgE介导的病症如哮喘的方法。 所述方法包括向受试者施用治疗有效量的TSLP拮抗剂。 本文还公开了转基因小鼠。 这些小鼠的体细胞和生殖细胞包括破坏的胸腺基质淋巴细胞生成素受体(TSLP)基因,破坏足以抑制TSLP与其受体的相互作用,以及破坏的γ基因,破坏 足以减少信号通过伽马。 小鼠表现出胸腺细胞减少。 还公开了将这些小鼠用于药物筛选的方法。

    METHODS FOR USE OF TSLP AND AGONISTS AND ANTAGONISTS THEREOF
    2.
    发明申请
    METHODS FOR USE OF TSLP AND AGONISTS AND ANTAGONISTS THEREOF 有权
    使用TSLP和激动剂及其拮抗剂的方法

    公开(公告)号:US20070237787A1

    公开(公告)日:2007-10-11

    申请号:US11762357

    申请日:2007-06-13

    摘要: Methods are disclosed herein for specifically inducing proliferation of CD4+ T cells. The methods are of use in treating immunodeficiencies, such as an immunodeficiency produced by infection with an immunodeficiency virus, such as infection with a human immunodeficiency virus (HIV). The methods include contacting isolated mammalian CD4+ T cells with an effective amount of a thymic stromal derived lymphopoietin (TSLP) polypeptide or a therapeutically effective amount of nucleic acid encoding the TSLP polypeptide, thereby inducing proliferation of the T cells. Methods are also disclosed for treating an IgE mediated disorder, such as asthma. The methods include administering to a subject a therapeutically effective amount of a TSLP antagonist. Transgenic mice are also disclosed herein. The somatic and germ cells of these mice include a disrupted thymic stromal lymphopoietin receptor (TSLP) gene, the disruption being sufficient to inhibit the interaction of TSLP with its receptor, and a disrupted γc gene, the disruption being sufficient to reduce signaling through the γc. The mice exhibit diminished thymic cellularity. Methods of using these mice for drug screening are also disclosed.

    摘要翻译: 本文公开了用于特异性诱导CD4 + T细胞增殖的方法。 该方法可用于治疗免疫缺陷,例如由免疫缺陷病毒感染产生的免疫缺陷,例如人免疫缺陷病毒(HIV)的感染。 所述方法包括使分离的哺乳动物CD4 + T细胞与有效量的胸腺基质衍生的淋巴细胞生成素(TSLP)多肽或治疗有效量的编码TSLP多肽的核酸接触,从而诱导T细胞的增殖。 还公开了用于治疗IgE介导的病症如哮喘的方法。 所述方法包括向受试者施用治疗有效量的TSLP拮抗剂。 本文还公开了转基因小鼠。 这些小鼠的体细胞和生殖细胞包括破坏的胸腺基质淋巴细胞生成素受体(TSLP)基因,破坏足以抑制TSLP与其受体的相互作用,以及破坏的γ基因,破坏 足以减少信号通过伽马。 小鼠表现出胸腺细胞减少。 还公开了将这些小鼠用于药物筛选的方法。

    Methods for use of TSLP and agonists and antagonists thereof
    3.
    发明授权
    Methods for use of TSLP and agonists and antagonists thereof 有权
    使用TSLP及其激动剂及其拮抗剂的方法

    公开(公告)号:US07731953B2

    公开(公告)日:2010-06-08

    申请号:US11762357

    申请日:2007-06-13

    IPC分类号: A01N63/00 C12N5/071

    摘要: Methods are disclosed herein for specifically inducing proliferation of CD4+ T cells. The methods are of use in treating immunodeficiencies, such as an immunodeficiency produced by infection with an immunodeficiency virus, such as infection with a human immunodeficiency virus (HIV). The methods include contacting isolated mammalian CD4+ T cells with an effective amount of a thymic stromal derived lymphopoietin (TSLP) polypeptide or a therapeutically effective amount of nucleic acid encoding the TSLP polypeptide, thereby inducing proliferation of the T cells. Methods are also disclosed for treating an IgE mediated disorder, such as asthma. The methods include administering to a subject a therapeutically effective amount of a TSLP antagonist. Transgenic mice are also disclosed herein. The somatic and germ cells of these mice include a disrupted thymic stromal lymphopoietin receptor (TSLP) gene, the disruption being sufficient to inhibit the interaction of TSLP with its receptor, and a disrupted γc gene, the disruption being sufficient to reduce signaling through the γc. The mice exhibit diminished thymic cellularity. Methods of using these mice for drug screening are also disclosed.

    摘要翻译: 本文公开了特异性诱导CD4 + T细胞增殖的方法。 该方法可用于治疗免疫缺陷,例如由免疫缺陷病毒感染产生的免疫缺陷,例如人免疫缺陷病毒(HIV)的感染。 所述方法包括使分离的哺乳动物CD4 + T细胞与有效量的胸腺基质衍生的淋巴细胞生成素(TSLP)多肽或治疗有效量的编码TSLP多肽的核酸接触,从而诱导T细胞的增殖。 还公开了用于治疗IgE介导的病症如哮喘的方法。 所述方法包括向受试者施用治疗有效量的TSLP拮抗剂。 本文还公开了转基因小鼠。 这些小鼠的体细胞和生殖细胞包括破坏的胸腺基质淋巴细胞生成素受体(TSLP)基因,破坏足以抑制TSLP与其受体的相互作用,以及破坏的γc基因,破坏足以减少通过γc的信号转导 。 小鼠表现出胸腺细胞减少。 还公开了将这些小鼠用于药物筛选的方法。

    Method of inducing memory B cell development and terminal differentiation
    4.
    发明申请
    Method of inducing memory B cell development and terminal differentiation 有权
    诱导记忆B细胞发育和终末分化的方法

    公开(公告)号:US20060057123A1

    公开(公告)日:2006-03-16

    申请号:US11197221

    申请日:2005-08-03

    IPC分类号: A61K35/14 C12N5/08

    摘要: A method is disclosed herein for inducing differentiation of a B cell progenitor into a memory B cells and/or a plasma cell. The method includes contacting a population of cells including a mature B cell or a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. In one embodiment, the B cell progenitor is an immature B cell. A method is also disclosed for enhancing an immune response. The method includes contacting a population of cells including a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. The memory B cells and/or the plasma cell are then introduced into the subject to enhance the immune response. A method is also disclosed for treating a subject with a condition comprising a specific deficiency of at least one of memory B cells and plasma cells. A method is disclosed for identifying an agent with a physiological effect on one or more of a memory B cell and a plasma cell differentiation. A method is also disclosed for identifying agents that inhibit an activity of IL-21. Methods are also disclosed for inducing apoptosis of a B cell and for decreasing the number of B cells. A method is also described for producing a B cell hybridoma.

    摘要翻译: 本文公开了一种用于诱导B细胞祖细胞分化为记忆B细胞和/或浆细胞的方法。 该方法包括使包含成熟B细胞或B细胞祖细胞的细胞群与有效量的IL-21接触,并分离记忆B细胞或浆细胞。 在一个实施方案中,B细胞祖细胞是未成熟B细胞。 还公开了一种用于增强免疫应答的方法。 该方法包括使包含B细胞祖细胞的细胞群与有效量的IL-21接触,并分离记忆B细胞或浆细胞。 然后将记忆B细胞和/或浆细胞引入受试者以增强免疫应答。 还公开了一种用于治疗患有包含存储B细胞和浆细胞中的至少一种的特定缺陷的病症的受试者的方法。 公开了用于鉴定对存储B细胞和浆细胞分化中的一种或多种具有生理作用的药剂的方法。 还公开了用于鉴定抑制IL-21活性的试剂的方法。 还公开了诱导B细胞凋亡和减少B细胞数量的方法。 还描述了用于产生B细胞杂交瘤的方法。

    METHOD FOR TREATING CANCER IN HUMANS
    5.
    发明申请
    METHOD FOR TREATING CANCER IN HUMANS 审中-公开
    人类治疗癌症的方法

    公开(公告)号:US20100135958A1

    公开(公告)日:2010-06-03

    申请号:US12651858

    申请日:2010-01-04

    摘要: A method of treating and/or preventing cancer in a subject, preferably mammalian, more preferably human, by administering in an effective amount IL-21 polypeptide, polynucleotide, vector comprising an IL-21 nucleic acid sequence encoding an IL-21 polypeptide, variants, and fragments thereof, thereby acting as an anti-cancer agent by reducing, ameliorating, and/or eliminating the cancer; and a method of treating and/or preventing cancer in a subject by co-administering the IL-21 polypeptide, polynucleotide, IL-21 vector, variant, and fragments thereof, with an immunotherapeutic and/or chemotherapeutic agent for the treatment and/or prevention of cancer in a subject.

    摘要翻译: 通过施用有效量的IL-21多肽,多核苷酸,包含编码IL-21多肽的IL-21核酸序列的载体的载体,变体(或其组合)的变体,治疗和/或预防受试者,优选哺乳动物,更优选人的癌症的方法 及其片段,从而通过减少,改善和/或消除癌症作为抗癌剂; 以及通过与用于治疗和/或免疫治疗的免疫治疗剂和/或化学治疗剂共同施用IL-21多肽,多核苷酸,IL-21载体,变体及其片段来治疗和/或预防受试者的癌症的方法。 预防受试者的癌症。

    Method of inducing memory b cell development and terminal differentiation
    6.
    发明申请
    Method of inducing memory b cell development and terminal differentiation 有权
    诱导记忆b细胞发育和终末分化的方法

    公开(公告)号:US20070003515A1

    公开(公告)日:2007-01-04

    申请号:US10579988

    申请日:2004-11-18

    摘要: A method is disclosed herein for inducing differentiation of a B cell progenitor into a memory B cells and/or a plasma cell. The method includes contacting a population of cells including a mature B cell or a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. In one embodiment, the B cell progenitor is an immature B cell. A method is also disclosed for enhancing an immune response. The method includes contacting a population of cells including a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. The memory B cells arid/or the plasma cell are then introduced into the subject to enhance the immune response. A method is also disclosed for treating a subject with a condition comprising a specific deficiency of at least one of memory B cells and plasma cells. A method is disclosed for identifying an agent with a physiological effect on one or more of a memory B cell and a plasma cell differentiation. A method is also disclosed for identifying agents that inhibit an activity of IL-21.

    摘要翻译: 本文公开了一种用于诱导B细胞祖细胞分化为记忆B细胞和/或浆细胞的方法。 该方法包括使包含成熟B细胞或B细胞祖细胞的细胞群与有效量的IL-21接触,并分离记忆B细胞或浆细胞。 在一个实施方案中,B细胞祖细胞是未成熟B细胞。 还公开了一种用于增强免疫应答的方法。 该方法包括使包含B细胞祖细胞的细胞群与有效量的IL-21接触,并分离记忆B细胞或浆细胞。 然后将记忆B细胞和/或浆细胞引入受试者以增强免疫应答。 还公开了一种用于治疗患有包含存储B细胞和浆细胞中的至少一种的特定缺陷的病症的受试者的方法。 公开了用于鉴定对存储B细胞和浆细胞分化中的一种或多种具有生理作用的药剂的方法。 还公开了用于鉴定抑制IL-21活性的试剂的方法。

    IL-21 as a regulator of immunoglobin production
    7.
    发明申请
    IL-21 as a regulator of immunoglobin production 有权
    IL-21作为免疫球蛋白生产的调节剂

    公开(公告)号:US20050193434A1

    公开(公告)日:2005-09-01

    申请号:US11027868

    申请日:2004-12-30

    摘要: A transgenic mouse is disclosed herein whose somatic and germ cells comprise a disrupted IL-21 receptor gene, the disruption being sufficient to inhibit the binding of IL-21 to an IL-21 receptor, and a disrupted IL-4 gene, the disruption being sufficient to inhibit the production of IL-4 or the binding of IL-4 to the IL-4 receptor. A mouse homozygous for the disrupted IL-21 receptor gene and homozygous for the disrupted IL-4 gene has diminished B cell function. A method is disclosed for altering a B cell activity. The method includes administering a therapeutically effective amount of an agent that interferes with the interaction of IL-21 with an IL-21 receptor, thereby altering the B cell activity. A method is also disclosed for of treating a subject with Job's disorder or atopic disease. A method is also disclosed for treating or preventing an allergic reaction in a subject. A method is also disclosed for treating a subject with an autoimmune or antibody mediated disorder.

    摘要翻译: 本文公开了一种转基因小鼠,其体细胞和生殖细胞包含破坏的IL-21受体基因,所述破坏足以抑制IL-21与IL-21受体的结合以及破坏的IL-4基因,所述破坏是 足以抑制IL-4的产生或IL-4与IL-4受体的结合。 对于破坏的IL-21受体基因纯合的小鼠和破坏的IL-4基因是纯合的,具有减少的B细胞功能。 公开了用于改变B细胞活性的方法。 该方法包括施用治疗有效量的干扰IL-21与IL-21受体相互作用的试剂,由此改变B细胞活性。 还公开了用于治疗患有约瑟病或特应性疾病的受试者的方法。 还公开了用于治疗或预防受试者的过敏反应的方法。 还公开了用自身免疫或抗体介导的病症治疗受试者的方法。

    METHOD OF INDUCING MEMORY B CELL DEVELOPMENT AND TERMINAL DIFFERENTIATION
    8.
    发明申请
    METHOD OF INDUCING MEMORY B CELL DEVELOPMENT AND TERMINAL DIFFERENTIATION 有权
    诱导记忆B细胞发育和终末分化的方法

    公开(公告)号:US20080305076A1

    公开(公告)日:2008-12-11

    申请号:US12126166

    申请日:2008-05-23

    摘要: A method is disclosed herein for inducing differentiation of a B cell progenitor into a memory B cells and/or a plasma cell. The method includes contacting a population of cells including a mature B cell or a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. In one embodiment, the B cell progenitor is an immature B cell. A method is also disclosed for enhancing an immune response. The method includes contacting a population of cells including a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. The memory B cells and/or the plasma cell are then introduced into the subject to enhance the immune response. A method is also disclosed for treating a subject with a condition comprising a specific deficiency of at least one of memory B cells and plasma cells. A method is disclosed for identifying an agent with a physiological effect on one or more of a memory B cell and a plasma cell differentiation. A method is also disclosed for identifying agents that inhibit an activity of IL-21. Methods are also disclosed for inducing apoptosis of a B cell and for decreasing the number of B cells. A method is also described for producing a B cell hybridoma.

    摘要翻译: 本文公开了一种用于诱导B细胞祖细胞分化为记忆B细胞和/或浆细胞的方法。 该方法包括使包含成熟B细胞或B细胞祖细胞的细胞群与有效量的IL-21接触,并分离记忆B细胞或浆细胞。 在一个实施方案中,B细胞祖细胞是未成熟B细胞。 还公开了一种用于增强免疫应答的方法。 该方法包括使包含B细胞祖细胞的细胞群与有效量的IL-21接触,并分离记忆B细胞或浆细胞。 然后将记忆B细胞和/或浆细胞引入受试者以增强免疫应答。 还公开了一种用于治疗患有包含存储B细胞和浆细胞中的至少一种的特定缺陷的病症的受试者的方法。 公开了用于鉴定对存储B细胞和浆细胞分化中的一种或多种具有生理作用的药剂的方法。 还公开了用于鉴定抑制IL-21活性的试剂的方法。 还公开了诱导B细胞凋亡和减少B细胞数量的方法。 还描述了用于产生B细胞杂交瘤的方法。

    Method of inducing memory B cell development and terminal differentiation
    9.
    发明授权
    Method of inducing memory B cell development and terminal differentiation 有权
    诱导记忆B细胞发育和终末分化的方法

    公开(公告)号:US07378276B2

    公开(公告)日:2008-05-27

    申请号:US11197221

    申请日:2005-08-03

    摘要: A method is disclosed herein for inducing differentiation of a B cell progenitor into a memory B cells and/or a plasma cell. The method includes contacting a population of cells including a mature B cell or a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. In one embodiment, the B cell progenitor is an immature B cell. A method is also disclosed for enhancing an immune response. The method includes contacting a population of cells including a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. The memory B cells and/or the plasma cell are then introduced into the subject to enhance the immune response. A method is also disclosed for treating a subject with a condition comprising a specific deficiency of at least one of memory B cells and plasma cells. A method is disclosed for identifying an agent with a physiological effect on one or more of a memory B cell and a plasma cell differentiation. A method is also disclosed for identifying agents that inhibit an activity of IL-21. Methods are also disclosed for inducing apoptosis of a B cell and for decreasing the number of B cells. A method is also described for producing a B cell hybridoma.

    摘要翻译: 本文公开了一种用于诱导B细胞祖细胞分化为记忆B细胞和/或浆细胞的方法。 该方法包括使包含成熟B细胞或B细胞祖细胞的细胞群与有效量的IL-21接触,并分离记忆B细胞或浆细胞。 在一个实施方案中,B细胞祖细胞是未成熟的B细胞。 还公开了一种用于增强免疫应答的方法。 该方法包括使包含B细胞祖细胞的细胞群与有效量的IL-21接触,并分离记忆B细胞或浆细胞。 然后将记忆B细胞和/或浆细胞引入受试者以增强免疫应答。 还公开了一种用于治疗患有包含存储B细胞和浆细胞中的至少一种的特定缺陷的病症的受试者的方法。 公开了用于鉴定对存储B细胞和浆细胞分化中的一种或多种具有生理作用的药剂的方法。 还公开了用于鉴定抑制IL-21活性的试剂的方法。 还公开了诱导B细胞凋亡和减少B细胞数量的方法。 还描述了用于产生B细胞杂交瘤的方法。

    Method of inducing memory B cell development and terminal differentiation
    10.
    发明授权
    Method of inducing memory B cell development and terminal differentiation 有权
    诱导记忆B细胞发育和终末分化的方法

    公开(公告)号:US07993919B2

    公开(公告)日:2011-08-09

    申请号:US10579988

    申请日:2004-11-18

    IPC分类号: C12N5/00 C12N5/071

    摘要: A method is disclosed herein for inducing differentiation of a B cell progenitor into a memory B cells and/or a plasma cell. The method includes contacting a population of cells including a mature B cell or a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. In one embodiment, the B cell progenitor is an immature B cell. A method is also disclosed for enhancing an immune response. The method includes contacting a population of cells including a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. The memory B cells arid/or the plasma cell are then introduced into the subject to enhance the immune response. A method is also disclosed for treating a subject with a condition comprising a specific deficiency of at least one of memory B cells and plasma cells. A method is disclosed for identifying an agent with a physiological effect on one or more of a memory B cell and a plasma cell differentiation. A method is also disclosed for identifying agents that inhibit an activity of IL-21.

    摘要翻译: 本文公开了一种用于诱导B细胞祖细胞分化为记忆B细胞和/或浆细胞的方法。 该方法包括使包含成熟B细胞或B细胞祖细胞的细胞群与有效量的IL-21接触,并分离记忆B细胞或浆细胞。 在一个实施方案中,B细胞祖细胞是未成熟B细胞。 还公开了一种用于增强免疫应答的方法。 该方法包括使包含B细胞祖细胞的细胞群与有效量的IL-21接触,并分离记忆B细胞或浆细胞。 然后将记忆B细胞和/或浆细胞引入受试者以增强免疫应答。 还公开了一种用于治疗患有包含存储B细胞和浆细胞中的至少一种的特定缺陷的病症的受试者的方法。 公开了用于鉴定对存储B细胞和浆细胞分化中的一种或多种具有生理作用的药剂的方法。 还公开了用于鉴定抑制IL-21活性的试剂的方法。