TARGETING AND THERAPY OF TUMORS WITH MONOCLONAL ANTIBODY

抗人源性大肠杆菌单克隆抗体F36/22和M7/105 乳腺癌细胞 这些抗体定位人类肿瘤异种移植物 其特异性表达相应的靶抗原。 当 被动给药，这些单克隆抗体产生快速和高度显着的 减少植入的逐渐生长的人类肿瘤的体积， 无胸腺小鼠 这项研究的目的是扩大这些 关于人肿瘤的体内靶向和治疗的观察 从原发性肿瘤外植体产生并表征的异种移植物 细胞系 被动给药的最佳治疗效果 和药物偶联抗体将进行以下评估 参数，使用肿瘤体积减小作为终点： 抗原表达; 2）抗体的剂量和时间表; 3）初始 肿瘤体积; 4）肿瘤的初始生长速率; 5）存在或 无转移; 6）多种单抗联合应用。 研究 对单克隆抗体将核磁共振密集物质运送到肿瘤部位的能力的研究将 也可以执行。 以组织定位指数为终点， 与铁-56和氟-19金属螯合物结合的单克隆抗体将被 给药至携带人肿瘤异种移植物的动物。 单克隆抗体也将 评估其特异性去除癌细胞的能力， 骨髓，作为未来自体骨髓抢救的先决条件。

Monoclonal antibodies F36/22 and M7/l05 have been raised against human breast carcinoma cells. These antibodies localize human tumor xenografts which specifically express the corresponding target antigens. When passively administered, these McAbs produce a rapid and highly significant reduction in the volume of progressively growing human tumors implanted in athymic mice. The purpose of the proposed research is to extend these observations regarding the in vivo targeting and therapy of human tumor xenografts as generated both from primary tumor explants and characterized cell lines. The optimal therapeutic efficacies of passively-administered and drug-conjugated antibodies will be assessed regarding the following parameters, using tumor volume reduction as the endpoint: l) levels of antigen expression; 2) dosage and scheduling of antibodies; 3) initial tumor volume; 4) initial growth rate of the tumor; 5) the presence or absence of metastasis; and 6) the combined use of multiple McAbs. Studies on the ability of McAbs to deliver NMR-dense substances to tumor sites will also be performed. Using the tissue localization index as the endpoint, McAbs conjugated to iron-56 and fluorine-l9 metal chelates will be administered to animals bearing human tumor xenografts. McAbs will also be evaluated for their capacity to specifically remove carcinoma cells from bone marrow, as a pre-requisite for future autologous bone marrow rescue.