公开(公告)号：US06797702B1

公开(公告)日：2004-09-28

申请号：US08918407

申请日：1997-08-26

申请人： Jack A. Roth ,  Toshiyoshi Fujiwara ,  Elizabeth A. Grimm ,  Tapas Mukhopadhyay ,  Wei-Wei Zhang ,  Laurie B. Owen-Schaub

发明人： Jack A. Roth ,  Toshiyoshi Fujiwara ,  Elizabeth A. Grimm ,  Tapas Mukhopadhyay ,  Wei-Wei Zhang ,  Laurie B. Owen-Schaub

IPC分类号： A61K31713

CPC分类号： C07K14/82 ,  A61K31/4745 ,  A61K31/513 ,  A61K31/704 ,  A61K31/7048 ,  A61K31/7072 ,  A61K33/24 ,  A61K38/00 ,  A61K45/06 ,  A61K48/00 ,  C07K14/4746 ,  C12N15/1135 ,  C12N15/86 ,  C12N2710/10332 ,  C12N2710/10343 ,  C12N2799/022

摘要： The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

摘要翻译： 本发明涉及肿瘤抑制基因与DNA损伤剂或因子组合使用，用于杀死细胞，特别是癌细胞。 肿瘤抑制基因p53通过体外和体内的重组腺病毒介导的基因转移与化学治疗剂组合递送。 经特异性DNA断裂处理的细胞经历凋亡。 将p53腺病毒构建体直接注射入肿瘤皮下，然后腹膜内施用DNA损伤剂顺铂，诱导肿瘤的大量凋亡破坏。 本发明还提供了使用复制缺陷型野生型p53腺病毒和DNA损伤药物治疗人类癌症的组合基因置换方案的临床应用。

公开(公告)号：US07109179B2

公开(公告)日：2006-09-19

申请号：US10784538

申请日：2004-02-23

申请人： Jack A. Roth ,  Toshiyoshi Fujiwara ,  Elizabeth A. Grimm ,  Tapas Mukhopadhyay ,  Wei-Wei Zhang ,  Laurie B. Owen-Schaub

发明人： Jack A. Roth ,  Toshiyoshi Fujiwara ,  Elizabeth A. Grimm ,  Tapas Mukhopadhyay ,  Wei-Wei Zhang ,  Laurie B. Owen-Schaub

IPC分类号： A61K31/713

CPC分类号： C07K14/82 ,  A61K31/4745 ,  A61K31/513 ,  A61K31/704 ,  A61K31/7048 ,  A61K31/7072 ,  A61K33/24 ,  A61K38/00 ,  A61K45/06 ,  A61K48/00 ,  C07K14/4746 ,  C12N15/1135 ,  C12N15/86 ,  C12N2710/10332 ,  C12N2710/10343 ,  C12N2799/022

摘要： The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

公开(公告)号：US6069134A

公开(公告)日：2000-05-30

申请号：US953290

申请日：1997-10-17

申请人： Jack A. Roth ,  Toshiyoshi Fujiwara ,  Elizabeth A. Grimm ,  Tapas Mukhopadhyay ,  Wei-Wei Zhang ,  Laurie B. Owen-Schaub

发明人： Jack A. Roth ,  Toshiyoshi Fujiwara ,  Elizabeth A. Grimm ,  Tapas Mukhopadhyay ,  Wei-Wei Zhang ,  Laurie B. Owen-Schaub

IPC分类号： C12N15/09 ,  A61K9/08 ,  A61K31/277 ,  A61K31/40 ,  A61K31/407 ,  A61K31/4745 ,  A61K31/505 ,  A61K31/513 ,  A61K31/70 ,  A61K31/704 ,  A61K31/7048 ,  A61K31/711 ,  A61K33/24 ,  A61K35/76 ,  A61K38/00 ,  A61K38/17 ,  A61K45/00 ,  A61K48/00 ,  A61K51/00 ,  A61P35/00 ,  C07K14/47 ,  C07K14/82 ,  C12N15/113 ,  C12N15/861

CPC分类号： C07K14/82 ,  A61K31/4745 ,  A61K31/513 ,  A61K31/704 ,  A61K31/7048 ,  A61K31/7072 ,  A61K33/24 ,  A61K45/06 ,  A61K48/00 ,  C07K14/4746 ,  C12N15/1135 ,  C12N15/86 ,  A61K38/00 ,  C12N2710/10332 ,  C12N2710/10343 ,  C12N2799/022

摘要： The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

摘要翻译： 本发明涉及肿瘤抑制基因与DNA损伤剂或因子组合使用，用于杀死细胞，特别是癌细胞。 肿瘤抑制基因p53通过体外和体内的重组腺病毒介导的基因转移与化学治疗剂组合递送。 经特异性DNA断裂处理的细胞经历凋亡。 将p53腺病毒构建体直接注射入肿瘤皮下，然后腹膜内施用DNA损伤剂顺铂，诱导肿瘤的大量凋亡破坏。 本发明还提供了使用复制缺陷型野生型p53腺病毒和DNA损伤药物治疗人类癌症的组合基因置换方案的临床应用。

公开(公告)号：US5747469A

公开(公告)日：1998-05-05

申请号：US233002

申请日：1994-04-25

申请人： Jack A. Roth ,  Toshiyoshi Fujiwara ,  Elizabeth A. Grimm ,  Tapas Mukhopadhyay ,  Wei-Wei Zhang ,  Laurie B. Owen-Schaub

发明人： Jack A. Roth ,  Toshiyoshi Fujiwara ,  Elizabeth A. Grimm ,  Tapas Mukhopadhyay ,  Wei-Wei Zhang ,  Laurie B. Owen-Schaub

IPC分类号： C12N15/09 ,  A61K9/08 ,  A61K31/277 ,  A61K31/40 ,  A61K31/407 ,  A61K31/4745 ,  A61K31/505 ,  A61K31/513 ,  A61K31/70 ,  A61K31/704 ,  A61K31/7048 ,  A61K31/711 ,  A61K33/24 ,  A61K35/76 ,  A61K38/00 ,  A61K38/17 ,  A61K45/00 ,  A61K48/00 ,  A61K51/00 ,  A61P35/00 ,  C07K14/47 ,  C07K14/82 ,  C12N15/113 ,  C12N15/861 ,  C12N5/00 ,  C12N15/00

CPC分类号： C07K14/82 ,  A61K31/4745 ,  A61K31/513 ,  A61K31/704 ,  A61K31/7048 ,  A61K31/7072 ,  A61K33/24 ,  A61K45/06 ,  A61K48/00 ,  C07K14/4746 ,  C12N15/1135 ,  C12N15/86 ,  A61K38/00 ,  C12N2710/10332 ,  C12N2710/10343 ,  C12N2799/022

摘要： The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

公开(公告)号：US5229109A

公开(公告)日：1993-07-20

申请号：US868765

申请日：1992-04-14

申请人： Elizabeth A. Grimm ,  Keith Heaton

发明人： Elizabeth A. Grimm ,  Keith Heaton

IPC分类号： C12N5/10 ,  A61K35/14 ,  A61K38/00 ,  A61P35/00 ,  A61P37/04 ,  C07K14/55

CPC分类号： C07K14/55 ,  A61K38/00

摘要： The properties of two recombinant human IL-2 analogues with mutations at Arginine 38 (.fwdarw.Alanine) and Phenylalanine 42 (.fwdarw.Lysine) were analyzed and compared to those of native IL-2. These analogues were found to maintain their ability to bind to the intermediate IL-2 receptor, p75, while binding only minimally to the high affinity p55+p75 receptor complex. The analogues also maintained the ability to stimulate peripheral blood mononuclear cells to generate lymphokine activated killing (LAK). However, IL-1.beta. and TNF-.alpha. secretion were significantly reduced in response to the analogues, as compared to the native IL-2 molecule. These analogues are therefore potentially valuable low-toxicity alternatives to IL-2 in human immunotherapy and adoptive immunotherapy treatment strategies.

摘要翻译： 分析了在精氨酸38（→丙氨酸）和苯丙氨酸42（ - >赖氨酸）上具有突变的两种重组人IL-2类似物的性质，并与天然IL-2的性质进行比较。 发现这些类似物保持其结合中间体IL-2受体p75的能力，同时仅结合高亲和力p55 + p75受体复合物。 类似物也保持刺激外周血单核细胞产生淋巴因子活化杀伤（LAK）的能力。 然而，与天然IL-2分子相比，对类似物的IL-1β和TNF-α分泌显着降低。 因此，这些类似物是人类免疫治疗和过继免疫治疗策略中IL-2的潜在有价值的低毒替代物。