公开(公告)号：US5641677A

公开(公告)日：1997-06-24

申请号：US288428

申请日：1994-08-10

申请人： Augusto Carlos Ochoa ,  Robin Lee Geller ,  Fritz H. Bach

发明人： Augusto Carlos Ochoa ,  Robin Lee Geller ,  Fritz H. Bach

IPC分类号： A61K9/127 ,  A61K35/12 ,  A61K35/14 ,  A61K35/17 ,  A61K38/20 ,  A61K39/00 ,  A61K39/395 ,  C07K16/28 ,  C12N5/00 ,  C12N5/02 ,  C12N5/0783 ,  C12N5/06

CPC分类号： C12N5/0087 ,  A61K35/17 ,  C07K16/2809 ,  C12N5/0636 ,  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., cytotoxicity, 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 cells are then cultured in the presence of interleukin-2 (IL-2) and an antibody to a lymphocyte surface receptor, preferably an anti-CD3 monoclonal antibody (MoAb). The present invention also provides a method of enhancing the immunotherapeutic activity, e.g., cytotoxicity, of immune cells by culturing immune cells in the presence of IL-2 and an antibody to a lymphocyte surface receptor, preferably an anti-CD3 MoAb; separating a cell subset capable of developing immunotherapeutic activity, e.g., cytotoxicity, from the cultured immune cells, e.g., either CD4.sup.+ or CD8.sup.+ lymphocytes; and then subculturing the separated lymphocytes in the presence of IL-2.

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（例如细胞毒性）的方法。 然后在白细胞介素-2（IL-2）和抗淋巴细胞表面受体的抗体（优选抗CD3单克隆抗体（MoAb））的存在下培养剩余的耗尽的免疫细胞。 本发明还提供了通过在IL-2和针对淋巴细胞表面受体，优选抗CD3 MoAb的抗体的存在下培养免疫细胞来增强免疫细胞的免疫治疗活性，例如细胞毒性的方法; 从培养的免疫细胞例如CD4 +或CD8 +淋巴细胞分离能够发展免疫治疗活性（例如细胞毒性）的细胞亚群; 然后在存在IL-2的情况下传代培养分离的淋巴细胞。

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。