HUMAN MONOCLONAL ANTIBODIES PRODUCED IN SCID MICE

一种产生人单克隆抗体的新方法将是 研究了C.B-17 scid/scid（SCID）小鼠将被植入人巨噬细胞。 外周血淋巴细胞（PBL）。这些动物将用 各种抗原，以激发人体的免疫反应， PBL。待测抗原包括：羊红细胞、葡聚糖、匙孔 以血蓝蛋白（KLH）为模型蛋白抗原， 二硝基苯酚和邻苯二甲酸酯与KLH结合，以及人肺肿瘤 细胞系A549。填充免疫动物脾脏的人PBL将 用PEG与鼠浆细胞瘤细胞系P3X63.Ag8.653融合， 并在含HAT的培养基中选择所得杂交瘤。生长 将筛选来自杂交培养物的培养基中是否存在 对免疫原有特异性的抗体阳性培养物将被克隆 有限稀释并重新测试抗体产生。人类起源 这些单克隆抗体将得到验证，其同种型 通过ELISA测定。可以预见，这种新的方法， 人单克隆抗体的产生将允许产生 针对大量相关抗原的单克隆抗体， 研究和克隆实验室，并将允许新的诊断和 治疗应用。

A novel approach to the generation of human monoclonal antibodies will be investigated. C.B-17scid/scid (SCID) mice will be engrafted with human peripheral blood lymphocytes (PBL). These animals will be immunized with a variety of antigens, in order to provoke an immune response by the human PBL. Antigens to be tested include: sheep red blood cells, dextran, keyhole limpet hemacyanin (KLH) as a model protein antigen, the haptens dinitrophenol and phthalate conjugated to KLH, and the human lung tumor cell line A549. Human PBL populating the spleen of immunized animals will be fused with the murine plasmacytoma cell line P3X63.Ag8.653 using PEG, and the resultant hybridomas selected in HAT-containing medium. The growth medium from hybridomacultures will be screened for the presence of antibodies specific for the immunogen. Positive cultures will be cloned by limiting dilution and retested for anti ' body production. The human origin of these monoclonal antibodies will be verified and their isotype determined by ELISA. It is anticipated that this novel approach to the generation of human monoclonal antibodies will allow the production of monoclonal antibodies against a vast array of antigens of relevance in the research and clonical laboratory and will allow new diagnostic and therapeutic applications.