Novel adenoviral vectors, packaging cell lines, recombinant adenoviruses and methods
    37.
    发明申请
    Novel adenoviral vectors, packaging cell lines, recombinant adenoviruses and methods 审中-公开
    新型腺病毒载体,包装细胞系,重组腺病毒和方法

    公开(公告)号:US20020168342A1

    公开(公告)日:2002-11-14

    申请号:US10036940

    申请日:2001-11-13

    摘要: The present invention is directed to novel replication-deficient adenoviral vectors characterized in that they harbor at least two lethal early region gene deletions (E1 and E4) that normally transcribe adenoviral early proteins. These novel recombinant vectors find particular use in human gene therapy treatment whereby the vectors additionally carry a transgene or therapeutic gene that replaces the E1 or E4 regions. The present invention is further directed to novel packaging cell lines that are transformed at a minimum with the adenoviral E1 and E4 gene regions and function to propagate the above novel replication-deficient adenoviral vectors.

    摘要翻译: 本发明涉及新型复制缺陷型腺病毒载体,其特征在于它们具有通常转录腺病毒早期蛋白质的至少两种致死性早期基因缺失(E1和E4)。 这些新型重组载体在人基因治疗治疗中特别有用,其中载体另外携带替代E1或E4区域的转基因或治疗基因。 本发明进一步涉及用腺病毒E1和E4基因区域最少转化的新型包装细胞系,并且其功能是增殖上述新的复制缺陷型腺病毒载体。

    Multispecific chimeric receptors
    38.
    发明授权
    Multispecific chimeric receptors 失效
    多特异性嵌合受体

    公开(公告)号:US6103521A

    公开(公告)日:2000-08-15

    申请号:US454098

    申请日:1995-05-30

    摘要: Novel multispecific chimeric receptor DNA sequences, expression cassettes and vectors containing these sequences as well as cells containing the chimeric DNA and novel chimeric receptor proteins expressed from the sequences are provided in the present invention. The novel multispecific chimeric receptor DNA and amino acid sequences comprise at least three domains that do not naturally exist together: (1) a multispecific binding domain comprising at least two extracellular inducer-responsive clustering domains which serves to bind at least one specific inducer molecule, (2) a transmembrane domain, which crosses the plasma membrane, and (3) either a proliferation signaling domain that signals the cell to divide, or an effector function signaling domain which directs a host cell to perform its specialized function. Optionally, all the multispecific chimeric receptors may contain one or more intracellular inducer-responsive clustering domains attached to one or more of the cytoplasmic signaling domains or the transmembrane domain. The present invention also relates to novel hybrid multispecific chimeric receptors comprising at least one proliferation signaling domain and at least one effector function signaling domain together on the multispecific receptor molecule. The present invention further relates to therapeutic methods and strategies that employ the cells expressing these novel chimeric receptors for the treatment of cancer, infectious disease and autoimmune disease which may have greater therapeutic benefit over a combination of drug therapies.

    摘要翻译: 在本发明中提供了新的多特异性嵌合受体DNA序列,表达盒和含有这些序列的载体以及含有嵌合DNA的细胞和由序列表达的新型嵌合受体蛋白。 新颖的多特异性嵌合受体DNA和氨基酸序列包含至少三个不天然存在的结构域:(1)多特异性结合结构域,其包含至少两个用于结合至少一个特异性诱导物分子的细胞外诱导物反应性聚簇结构域, (2)穿越质膜的跨膜结构域,和(3)信号细胞分裂的增殖信号转导域或引导宿主细胞执行其特异功能的效应子功能信号结构域。 任选地,所有多特异性嵌合受体可以含有连接至一个或多个胞质信号结构域或跨膜结构域的一个或多个细胞内诱导物反应性聚簇结构域。 本发明还涉及在多特异性受体分子上包含至少一个增殖信号结构域和至少一个效应子功能信号结构域的新型杂合多特异性嵌合受体。 本发明还涉及使用表达这些新型嵌合受体的细胞治疗癌症,感染性疾病和自身免疫疾病的治疗方法和策略,其可以比药物疗法的组合具有更大的治疗益处。

    DNA encoding an intracellular chimeric receptor comprising Janus kinase
    39.
    发明授权
    DNA encoding an intracellular chimeric receptor comprising Janus kinase 失效
    编码包含Janus激酶的细胞内嵌合受体的DNA

    公开(公告)号:US6077947A

    公开(公告)日:2000-06-20

    申请号:US485598

    申请日:1995-06-07

    摘要: The present invention is directed to novel chimeric proliferation receptor proteins and DNA sequences encoding these proteins where the chimeric proteins are characterized in three general categories. In one category, the novel chimeric proteins comprise at least three domains, namely, an extracellular inducer-responsive clustering domain capable of binding an extracellular inducer that transmits a signal to a proliferation signaling domain, a transmembrane domain and a proliferation signaling domain that signals a host cell to divide. In the second category, the novel chimeric proteins comprise at least two domains, namely, an intracellular inducer-responsive clustering domain capable of binding an intracellular inducer and a proliferation signaling domain that signals the cell to divide. In yet a third category, a novel hybrid chimeric protein receptor is contemplated that contains an intracellular or extracellular inducer domain, a transmembrane domain, a proliferation signaling domain and an effector signaling domain in a single chain molecule. Whether the binding domain is intracellular or extracellular, the binding of inducer to these novel chimeric receptor proteins induces the clustering of the binding domains to each other and further signals the cell to proliferate, and optionally, signal an effector function. The present invention further relates to expression vectors containing the nucleic acids encoding the novel chimeric receptors, cells expressing the novel chimeric receptors and therapeutic methods of using cells expressing these novel receptors for the treatment of cancer, infectious disease and autoimmune diseases, for example.

    摘要翻译: 本发明涉及嵌合增殖受体蛋白和编码这些蛋白的DNA序列,其中嵌合蛋白的特征在于三个一般类别。 在一个类别中,新型嵌合蛋白质包含至少三个结构域,即能够结合将信号传递给增殖信号转导域的细胞外诱导物 - 响应性聚簇结构域,跨膜结构域和增殖信号转导域, 宿主细胞分裂。 在第二类中,新的嵌合蛋白包含至少两个结构域,即能够结合细胞内诱导物的细胞内诱导物 - 响应聚簇结构域和信号细胞分裂的增殖信号转导域。 在三分之一类别中,预期在单链分子中含有细胞内或细胞外诱导物结构域,跨膜结构域,增殖信号结构域和效应子信号结构域的新型杂合嵌合蛋白受体。 结合结构域是细胞内还是细胞外,诱导物与这些新型嵌合受体蛋白的结合诱导结合结构域彼此聚集,并进一步使细胞信号增殖,并且任选地发送效应子功能。 本发明还涉及含有编码新型嵌合受体的核酸,表达新型嵌合受体的细胞和使用表达这些新受体的细胞治疗癌症,感染性疾病和自身免疫疾病的治疗方法的表达载体。