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    Methods of identifying patients having an altered immune status
    1.
    发明授权
    Methods of identifying patients having an altered immune status 失效
    识别具有改变的免疫状态的患者的方法

    公开(公告)号：US5658744A

    公开(公告)日：1997-08-19

    申请号：US277299

    申请日：1994-07-22

    申请人： Augusto C. Ochoa ,  Howard A. Young ,  Dan L. Longo ,  Paritosh Ghosh ,  Richard Robb ,  Mary Neville

    发明人： Augusto C. Ochoa ,  Howard A. Young ,  Dan L. Longo ,  Paritosh Ghosh ,  Richard Robb ,  Mary Neville

    IPC分类号： G01N33/53 ,  C12Q1/02 ,  C12Q1/24 ,  C12Q1/68 ,  G01N33/50 ,  G01N33/564 ,  G01N33/569 ,  G01N33/68

    CPC分类号： G01N33/68 ,  G01N33/5091 ,  G06F19/3431

    摘要： Methods of identifying a patient having an altered immune status involve determining an immune status index for the patient and comparing it to the immune status index in healthy individuals. In general, an immune status index is the ratio of the amount of a protein that varies significantly in a patient with an altered immune status to the amount of another protein that is substantially invariant in both healthy and immune-altered individuals. Variable proteins can be TCR subunit proteins, T lymphocyte signal transduction pathway proteins, polynucleotide binding proteins or biological response modifiers (BRM). In addition, the ratio of a TH-1-type BRM to a TH-2-type BRM, the ratio of cytoplasmic to nuclear levels of polynucleotide binding proteins, the pattern of protein binding to an oligonucleotide probe that comprises the protein binding region of a gene for a BRM, or the pattern of distribution of T lymphocytes in a density gradient following density gradient centrifugation are also suitable as an immune status index. The methods are useful in identifying patients exhibiting immunosuppression, hyperimmunity and autoimmunity, as well as in assessing the immune status of a patient undergoing organ transplant.

    摘要翻译： 识别具有改变的免疫状态的患者的方法包括确定患者的免疫状态指数并将其与健康个体的免疫状态指数进行比较。 通常，免疫状态指数是在具有改变的免疫状态的患者中显着变化的蛋白质的量与健康和免疫改变个体中基本上不变的另一蛋白质的量的比率。 可变蛋白可以是TCR亚基蛋白，T淋巴细胞信号转导通路蛋白，多核苷酸结合蛋白或生物反应调节剂（BRM）。 此外，TH-1型BRM与TH-2型BRM的比例，多核苷酸结合蛋白质的细胞质与核水平的比例，蛋白质与寡核苷酸探针结合的模式，其包含蛋白质结合区域 用于BRM的基因或密度梯度离心后的密度梯度中T淋巴细胞的分布模式也适合作为免疫状态指数。 该方法可用于鉴定表现出免疫抑制，超免疫和自身免疫的患者以及评估接受器官移植的患者的免疫状态。

    Methods of identifying patients having an altered immune status
    2.
    发明授权
    Methods of identifying patients having an altered immune status 失效
    识别具有改变的免疫状态的患者的方法

    公开(公告)号：US5965366A

    公开(公告)日：1999-10-12

    申请号：US880671

    申请日：1997-06-23

    申请人： Augusto C. Ochoa ,  Howard A. Young ,  Dan L. Longo ,  Paritosh Ghosh

    发明人： Augusto C. Ochoa ,  Howard A. Young ,  Dan L. Longo ,  Paritosh Ghosh

    IPC分类号： G01N33/53 ,  C12Q1/02 ,  C12Q1/24 ,  C12Q1/68 ,  G01N33/50 ,  G01N33/564 ,  G01N33/569 ,  G01N33/68

    CPC分类号： G01N33/68 ,  G01N33/5091 ,  G06F19/3431

    摘要： Methods of identifying a patient having an altered immune status involve determining an immune status index for the patient and comparing it to the immune status index in healthy individuals. In general, an immune status index is the ratio of the amount of a protein that varies significantly in a patient with an altered immune status to the amount of another protein that is substantially invariant in both healthy and immune-altered individuals. Variable proteins can be TCR subunit proteins, T lymphocyte signal transduction pathway proteins, polynucleotide binding proteins or biological response modifiers (BRM). In addition, the ratio of a TH-1-type BRM to a TH-2-type BRM, the ratio of cytoplasmic to nuclear levels of polynucleotide binding proteins, the pattern of protein binding to an oligonucleotide probe that comprises the protein binding region of a gene for a BRM, or the pattern of distribution of T lymphocytes in a density gradient following density gradient centrifugation are also suitable as an immune status index. The methods are useful in identifying patients exhibiting immunosuppression, hyperimmunity and autoimmunity, as well as in assessing the immune status of a patient undergoing organ transplant.

    摘要翻译： 识别具有改变的免疫状态的患者的方法包括确定患者的免疫状态指数并将其与健康个体的免疫状态指数进行比较。 通常，免疫状态指数是在具有改变的免疫状态的患者中显着变化的蛋白质的量与健康和免疫改变个体中基本上不变的另一蛋白质的量的比率。 可变蛋白可以是TCR亚基蛋白，T淋巴细胞信号转导通路蛋白，多核苷酸结合蛋白或生物反应调节剂（BRM）。 此外，TH-1型BRM与TH-2型BRM的比例，多核苷酸结合蛋白质的细胞质与核水平的比例，蛋白质与寡核苷酸探针结合的模式，其包含蛋白质结合区域 用于BRM的基因或密度梯度离心后的密度梯度中T淋巴细胞的分布模式也适合作为免疫状态指数。 该方法可用于鉴定表现出免疫抑制，超免疫和自身免疫的患者以及评估接受器官移植的患者的免疫状态。

    Evaluation and treatment of patients with progressive immunosuppression
    6.
    发明授权
    Evaluation and treatment of patients with progressive immunosuppression 失效
    进行性免疫抑制患者的评估和治疗

    公开(公告)号：US5583002A

    公开(公告)日：1996-12-10

    申请号：US987966

    申请日：1992-12-11

    申请人： Augusto C. Ochoa ,  Hiromoto Mizuguchi ,  John J. O'Shea ,  Dan L. Longo ,  Cynthia M. Loeffler

    发明人： Augusto C. Ochoa ,  Hiromoto Mizuguchi ,  John J. O'Shea ,  Dan L. Longo ,  Cynthia M. Loeffler

    IPC分类号： A61K38/00 ,  A61K38/20 ,  A61K39/00 ,  C07K14/47 ,  C07K16/18 ,  G01N33/574

    CPC分类号： C07K16/18 ,  A61K38/2013 ,  C07K14/4703 ,  A61K39/00

    摘要： A soluble immunosuppressive factor present in serum derived from tumor-bearing mammals, is associated with changes in TCR protein subunit levels and 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, or a protein in the T lymphocyte signal transduction pathway, and comparing the level 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蛋白亚基水平和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亚单位蛋白或T淋巴细胞信号转导途径中的蛋白质的表达水平，并将其水平与非淋巴细胞中发现的水平进行比较来确定哺乳动物免疫抑制水平的方法， 免疫抑制个体。 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。

    Method of treating tumors with CD8.sup.+ -depleted or CD4.sup.+ T cell subpopulations
    9.
    发明授权
    Method of treating tumors with CD8.sup.+ -depleted or CD4.sup.+ T cell subpopulations 失效
    用CD8 + - 剥离或CD4 + T细胞亚群治疗肿瘤的方法

    公开(公告)号：US5725855A

    公开(公告)日：1998-03-10

    申请号：US215767

    申请日：1994-03-22

    申请人： Augusto Carlos Ochoa ,  Mark L. Saxton ,  Dan L. Longo

    发明人： Augusto Carlos Ochoa ,  Mark L. Saxton ,  Dan L. Longo

    IPC分类号： C12P21/08 ,  A61K9/127 ,  A61K35/12 ,  A61K35/14 ,  A61K35/17 ,  A61K35/26 ,  A61K38/00 ,  A61K38/20 ,  A61K39/00 ,  A61K39/395 ,  A61P35/00 ,  C07K16/28 ,  C12N5/00 ,  C12N5/04 ,  C12N5/0783 ,  A61K35/28

    CPC分类号： C12N5/0636 ,  A61K31/675 ,  A61K35/17 ,  A61K35/26 ,  A61K38/2013 ,  C07K16/2809 ,  C12N5/0087 ,  A61K2039/5158 ,  A61K9/127 ,  C12N2501/125 ,  C12N2501/23 ,  C12N2501/515

    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.sup.+ or CD8.sup.+ 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竭的免疫细胞群体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。