TARGETING AND THERAPY OF TUMORS WITH MONOCLONAL ANTIBODY

已研制出针对人的单抗F36/22和M7/L05 乳腺癌细胞。这些抗体定位于人肿瘤移植瘤。 其特异性地表达相应的靶抗原。什么时候 被动给药，这些单抗产生快速和高度显著的 逐渐生长的人类肿瘤体积的缩小 无性系小鼠。拟议研究的目的是扩展这些 人体肿瘤体内靶向和治疗的观察 从原发肿瘤外植体产生的异种移植瘤 细胞系。被动给药的最佳治疗效果 和药物结合抗体将根据以下方面进行评估 参数，以肿瘤体积缩小为终点：L)水平 抗原表达；2)抗体的剂量和时间安排；3)初始 肿瘤体积；4)肿瘤的初始生长率；5)肿瘤的存在或 无转移；6)多种单抗联合应用。研究 关于单抗将核磁共振致密物质运送到肿瘤部位的能力 也会被执行。使用组织定位指数作为终点， 铁-56和氟-L9金属络合物的单抗将是 用于携带人类肿瘤异种移植瘤的动物。McAbs也将是 评估其特异性去除癌细胞的能力 骨髓，作为未来自体骨髓挽救的先决条件。

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.