TARGETED CELLULAR CYTOTOXICITY

靶向细胞毒性

• 批准号: 3774386
• 负责人: D M SEGAL
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3774386
• 关键词: CD3 molecule; T lymphocyte; antitumor antibody; antiviral antibody; cell mediated cytotoxicity; hybrid antibody; interleukin 2; leukocyte activation /transformation; mouse mammary tumor virus; neoplasm /cancer immunology; neoplasm /cancer transplantation

A murine breast cancer model has been developed for measuring the ability of targeted effector cells to eradicate primary and transplanted mammary tumors. Bispecific antibodies containing anti-CD3 cross linked to antibodies against gp52 from the mouse mammary tumor virus bind specifically to spontaneous or cultured mammary tumor cells, and induce murine T cells to lyse such cells in vitro and block the growth of subcutaneous tumor transplants in vivo. A genetically engineered bispecific F(ab')2 construct has been produced that has the same in vitro targeting activity as conventionally prepared bispecific antibodies. By using anti-CD44 containing bispecific antibodies, we have found that CD44 is a cytotoxic triggering molecule on a subset of human PBL. Cells mediating such targeted lysis reside in the LGL population, are CD56+, and are activated by IL-2.

已经开发了小鼠乳腺癌模型用于测量 靶向效应细胞，以根除原发性和移植性乳腺癌 肿瘤的含有交联的抗-CD 3的双特异性抗体 抗小鼠乳腺肿瘤病毒gp 52的抗体结合 特异性地针对自发的或培养的乳腺肿瘤细胞，并诱导 小鼠T细胞在体外裂解这种细胞，并阻断肿瘤细胞的生长。 体内皮下肿瘤移植。 基因工程 已经产生了双特异性F（ab '）2构建体，其在体外具有相同的生物活性。 靶向活性与常规制备的双特异性抗体相同。 通过使用含有抗CD 44的双特异性抗体，我们发现， CD 44是人PBL亚群上的细胞毒性触发分子。 细胞 介导这种靶向裂解的存在于LGL群体中的是CD 56+，和 被IL-2激活。