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    Tumor cells modified to express B7-2 with increased immunogenicity and uses therefor
    9.
    发明授权
    Tumor cells modified to express B7-2 with increased immunogenicity and uses therefor 失效
    肿瘤细胞修饰以表达B7-2，增加免疫原性，并用于此

    公开(公告)号：US06723705B1

    公开(公告)日：2004-04-20

    申请号：US09206132

    申请日：1998-12-07

    申请人： Gordon J. Freeman ,  Lee M. Nadler ,  Gary S. Gray

    发明人： Gordon J. Freeman ,  Lee M. Nadler ,  Gary S. Gray

    IPC分类号： A61K3170

    CPC分类号： A01K67/0271 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2267/0331 ,  A61K38/00 ,  C07K14/70532 ,  C07K16/2827 ,  C07K2319/00 ,  C07K2319/30 ,  C12N15/8509

    摘要： Tumor cells modified to express one or more T cell costimulatory molecules are disclosed. Preferred costimulatory molecules are B7-2 and B7-3. The tumor cells of the invention can be modified by transfection with nucleic acid encoding B7-2 and/or B7-3, by using an agent which induces or increases expression of B7-2 and/or B7-3 on the tumor cell or by coupling B7-2 and/or B7-3 to the tumor cell. Tumor cells modified to express B7-2 and/or B7-3 can be further modified to express B7. Tumor cells further modified to express MHC class I and/or class II molecules or in which expression of an MHC associated protein, the invariant chain, is inhibited are also disclosed. The modified tumor cells of the invention can be used in methods for treating a patient with a tumor, preventing or inhibiting metastatic spread of a tumor or preventing or inhibiting recurrence of a tumor. A method for specifically inducing a CD4+ T cell response against a tumor and a method for treating a tumor by modification of tumor cells in vivo are disclosed.

    摘要翻译： 公开了修饰以表达一种或多种T细胞共刺激分子的肿瘤细胞。 优选的共刺激分子是B7-2和B7-3。 本发明的肿瘤细胞可以通过用编码B7-2和/或B7-3的核酸转染，通过使用诱导或增加肿瘤细胞上B7-2和/或B7-3表达的试剂或通过 将B7-2和/或B7-3偶联到肿瘤细胞。 修饰以表达B7-2和/或B7-3的肿瘤细胞可进一步修饰以表达B7。 还公开了进一步修饰以表达MHC I类和/或II类分子或其中抑制MHC相关蛋白（不变链）的表达的肿瘤细胞。 本发明的修饰的肿瘤细胞可用于治疗患有肿瘤的患者，预防或抑制肿瘤的转移性扩散或预防或抑制肿瘤复发的方法。 公开了特异性诱导针对肿瘤的CD4 + T细胞应答的方法和通过体内修饰肿瘤细胞治疗肿瘤的方法。

    Fusion proteins of novel CTLA4/CD28 ligands and uses therefore
    10.
    发明授权
    Fusion proteins of novel CTLA4/CD28 ligands and uses therefore 失效
    新型CTLA4 / CD28配体的融合蛋白及其用途

    公开(公告)号：US06130316A

    公开(公告)日：2000-10-10

    申请号：US280757

    申请日：1994-07-26

    申请人： Gordon J. Freeman ,  Lee M. Nadler ,  Gary S. Gray ,  Edward Greenfield

    发明人： Gordon J. Freeman ,  Lee M. Nadler ,  Gary S. Gray ,  Edward Greenfield

    IPC分类号： A61K38/00 ,  C07K14/705 ,  C07K16/28 ,  C12N15/85 ,  C07K19/00 ,  C07H21/00

    CPC分类号： C07K16/2827 ,  C07K14/70532 ,  C12N15/8509 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2267/01 ,  A01K2267/03 ,  A01K2267/0381 ,  A61K38/00 ,  C07K2317/73 ,  C07K2319/00 ,  C07K2319/30

    摘要： Nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the nucleic acid has a sequence which encodes a B lymphocyte antigen, B7-2. Preferably, the nucleic acid is a DNA molecule comprising at least a portion of a nucleotide sequence shown in FIG. 8, SEQ ID NO:1 or FIG. 14, SEQ ID NO:23. The nucleic acid sequences of the invention can be integrated into various expression vectors, which in turn direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also disclosed are host cells transformed to produce proteins or peptides encoded by the nucleic acid sequences of the invention and isolated proteins and peptides which comprise at least a portion of a novel B lymphocyte antigen. Proteins and peptides described herein can be administered to subjects to enhance or suppress T cell-mediated immune responses.

    摘要翻译： 公开了编码协同T细胞活化的新型CTLA4 / CD28配体的核酸。 在一个实施方案中，核酸具有编码B淋巴细胞抗原B7-2的序列。 优选地，核酸是包含图1所示的核苷酸序列的至少一部分的DNA分子。 8，SEQ ID NO：1或图3。 14，SEQ ID NO：23。 本发明的核酸序列可以整合到各种表达载体中，这又指导了多种宿主，特别是真核细胞如哺乳动物和昆虫细胞培养物中的相应蛋白质或肽的合成。 还公开了转化以产生由本发明的核酸序列编码的蛋白质或肽的宿主细胞和包含至少一部分新型B淋巴细胞抗原的分离的蛋白质和肽。 本文所述的蛋白质和肽可以施用于受试者以增强或抑制T细胞介导的免疫应答。