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    • 2. 发明申请
    • Novel forms of T cell costimulatory molecules and uses therefor
    • 新型形式的T细胞共刺激分子及其用途
    • US20070106070A1
    • 2007-05-10
    • US11589275
    • 2006-10-26
    • Arlene SharpeFrancescopaolo BorrielloGordon FreemanLee Nadler
    • Arlene SharpeFrancescopaolo BorrielloGordon FreemanLee Nadler
    • C07H21/04
    • C07K14/70532A01K2217/05
    • Novel structural forms of T cell costimulatory molecules are described. These structural forms comprise a novel structural domain or have a structural domain deleted or added. The structural forms correspond to naturally-occurring alternatively spliced forms of T cell costimulatory molecules or variants thereof which can be produced by standard recombinant DNA techniques. In one embodiment, the T cell costimulatory molecule of the invention contains a novel cytoplasmic domain. In another embodiment, the T cell costimulatory molecule of the invention contains a novel signal peptide domain or has an immunoglobulin variable region-like domain deleted. The novel structural forms of T cell costimulatory molecules can be used to identify agents which stimulate the expression of alternative forms of costimulatory molecules and to identify components of the signal transduction pathway which results in costimulation of T cells.
    • 描述了T细胞共刺激分子的新型结构形式。 这些结构形式包括一个新的结构域或者具有缺失或添加的结构域。 结构形式对应于可以通过标准重组DNA技术产生的天然存在的可变剪接形式的T细胞共刺激分子或其变体。 在一个实施方案中,本发明的T细胞共刺激分子含有新的细胞质结构域。 在另一个实施方案中,本发明的T细胞共刺激分子含有新的信号肽结构域或具有免疫球蛋白可变区域结构域缺失。 T细胞共刺激分子的新型结构形式可用于鉴定刺激替代形式的共刺激分子表达的试剂,并鉴定导致T细胞共刺激的信号转导通路的成分。
    • 4. 发明申请
    • Tumor cells with increased immunogenicity and uses therfor
    • 肿瘤细胞具有增加的免疫原性,并使用其它药物
    • US20060099195A1
    • 2006-05-11
    • US11313556
    • 2005-12-20
    • Suzanne Ostrand-RosenbergSivasubramanian BaskarLaurie GlimcherGordon FreemanLee Nadler
    • Suzanne Ostrand-RosenbergSivasubramanian BaskarLaurie GlimcherGordon FreemanLee Nadler
    • A61K48/00
    • A61K39/0011A61K39/00A61K48/00A61K2039/5152A61K2039/5156A61K2039/5158C07K14/70532C07K14/70539
    • Tumor cells modified to express a T cell costimulatory molecule are disclosed. In one embodiment, the costimulatory molecule is a CD28/CTLA4 ligand, preferably a B lymphocyte antigen B7. The tumor cells of the invention can be modified by transfection with nucleic acid encoding a T cell costimulatory molecule, by using an agent which induces or increases expression of a T cell costimulatory molecule on the tumor cell surface or by coupling a T cell costimulatory molecule to the tumor cell surface. 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.
    • 公开了修饰以表达T细胞共刺激分子的肿瘤细胞。 在一个实施方案中,共刺激分子是CD28 / CTLA4配体,优选B淋巴细胞抗原B7。 通过使用诱导或增加T细胞共刺激分子在肿瘤细胞表面上的表达或通过将T细胞共刺激分子与T细胞共刺激分子的偶联的试剂,可以通过用编码T细胞共刺激分子的核酸转染来修饰本发明的肿瘤细胞 肿瘤细胞表面。 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。
    • 7. 发明申请
    • Tumor cells modified to express B7-2 with increased immunogenicity and uses therefor
    • 肿瘤细胞修饰以表达B7-2,增加免疫原性,并用于此
    • US20050129670A1
    • 2005-06-16
    • US10767561
    • 2004-01-28
    • Gordon FreemanLee NadlerGary Gray
    • Gordon FreemanLee NadlerGary Gray
    • A01K67/027A61K38/00C07K14/705C07K16/28C12N15/85A61K48/00
    • C12N15/8509A01K67/0271A01K2217/05A01K2227/105A01K2267/03A61K38/00C07K14/70532C07K16/2827C07K2319/00C07K2319/30
    • 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.
    • 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。