CELL MEDIATED CYTOTOXICITY

细胞介导的细胞毒性

• 批准号: 3962934
• 负责人: J R WUNDERLICH
• 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/3962934
• 关键词: T lymphocyte; cell cell interaction; cell differentiation; cell mediated cytotoxicity; cellular immunity; density gradient ultracentrifugation; genetic regulation; genetic strain; growth factor; immunogenetics; immunosuppression; immunotoxicity; interleukin 2; neoplasm /cancer genetics; neoplasm /cancer immunology; neoplastic cell; poly IC; radiotracer; sarcoma; sedimentation; spleen; tissue /cell culture

The cellular basis for in vitro generation of activated killer cells against tumors has been partially established, using polyinosinic acid (Poly I) and purified recombinant IL-2 as the activating agents. Precursor cells, which include both Thy 1+ and Thy 1- cells are stimulated by IL-2 and probably by additional lymphokines produced by accessory (macrophage and/or B cells) cells and L3T4+ helper T cells. The generation of anti-tumor cytotoxic cells is inhibited in a strain-dependent fashion by accessory cells. Together, low doses of IL-2 and ancillary activating agents (e.g., Poly I) generate levels of anti-tumor activity equivalent to those generated by high doses of IL-2 alone. Human PBL, activated in vitro with IL-2 and treated with hybrid monoclonal antibodies, block growth of human colon carcinoma cells in tumor neutralization assays in nude mice. The hybrid molecules consist of cross-linked monoclonal antibodies, which react 1) with immunoglobulin Fc receptors on K cells or with the antigen receptor complex on cytotoxic T lymphocytes and 2) with human colon carcinoma cells.

体外生成活化杀伤细胞的细胞基础 使用聚肌苷酸对抗肿瘤已部分确立 (Poly I)和纯化的重组IL-2作为激活剂。 前体 细胞（包括 Thy 1+ 和 Thy 1- 细胞）受到 IL-2 刺激 可能是由辅助细胞（巨噬细胞）产生的额外淋巴因子 和/或 B 细胞）细胞和 L3T4+ 辅助 T 细胞。 的一代 抗肿瘤细胞毒性细胞以菌株依赖性方式受到抑制 辅助细胞。 低剂量的 IL-2 和辅助激活一起 药剂（例如 Poly I）产生的抗肿瘤活性水平相当于 那些仅由高剂量的IL-2产生的。 人 PBL，在体外用 IL-2 激活并用杂合单克隆抗体处理 抗体，阻止肿瘤中人类结肠癌细胞的生长 裸鼠中和试验。 杂化分子组成为 交联单克隆抗体，与免疫球蛋白 Fc 发生反应 1) K 细胞上的受体或与细胞毒性 T 上的抗原受体复合物 淋巴细胞和2) 人结肠癌细胞。