RADIOIMMUNOTHERAPY OF BREAST CANCER

描述：(申请者摘要)该项目的长期目标是 开发放射免疫治疗(RIT)程序，用于治疗 播散性乳腺癌患者。具体目标是：1.开展临床工作 抗乳腺上皮粘蛋白抗体对乳腺癌的RIT研究 人源化BrE3(huBrE-3)。申请人启动了RIT第一阶段试验， 将继续增加(90)Y-huBrE-3 RIT和干细胞支持的剂量。 最后，它将为第二阶段的发展奠定基础。 将在随后迅速开发和启动的试验。HuBrE3和 I期和II期的结合物已经上市，临床上也有 该网站是一个经验丰富的RIT中心。2.准备人性化 抗乳胶粘附素抗体Hu-MC3，并启动成像研究。CGMP质量 将制备人源化huMc3(15克)，并与螯合物偶联 (111)In标记的MX-DTPA。一份类似于申请者已经 将开发使用(111)In-huBrE-3进行的成像试验。到目前为止， 已证明huBrE-3无毒，(111)In-huBrB3可能是 最好的乳房放射免疫显像剂。这是无可争议的 ~(90)Y-huBrE3也显示了特异性靶向能力，导致乳房变大 无毒副作用的肿瘤破坏。干细胞支持在HIS分期中的应用L RIT试验允许进一步的剂量升级和可能的大百分比 由于缺乏毒性和强大的杀瘤作用而引起的反应 到目前为止，最初低剂量的(90)Y-huBrE3。伴随而来的或 随后使用另一种抗乳腺癌抗体huMc3的RIT应该是 考虑到(90)Y-huBrE3的结果，进行了测试。发展选择性房地产投资信托基金 使用两种不同的乳房抗原可以提供协同作用的试剂 为了克服肿瘤细胞的异质性，抗体渗透和 最终提供足够的无毒治疗和可能的最终治愈 治疗转移性乳腺癌。

DESCRIPTION: (Applicant's Abstract) The long term objective of this project is to develop radioimmunotherapy (RIT) procedures for the treatment of disseminated breast cancer patients. The specific aims are: 1. Conduct clinical RIT studies on breast cancer with anti-Breast-Epithelial-Mucin (BEM) antibody, humanized BrE3 (huBrE-3). The applicant's initiated RIT Phase I trial with escalating doses of (90)Y-huBrE-3 RIT with stem cell support will be continued. It will provide, at its conclusion, the basis for the development of a Phase II trial that will be developed and initiated promptly afterwards. HuBrE3 and conjugates for the Phase I and II are already available as well as a clinical site that is a highly experienced RIT center. 2. Prepare humanized anti-lactadherin antibody hu-Mc3 and initiate imaging studies. cGMP quality humanized huMc3 will be prepared (15 gm) and conjugated with the chelate MX-DTPA labeled with (111)In. A protocol similar to the applicant's already performed imaging trial with (111)In-huBrE-3 will be developed. To date, huBrE-3 has been demonstrated to be non-toxic and (111)In-huBrB3 is possibly the best breast radioimmunoimaging reagent available. This indisputable specific targeting ability shown also by (90)Y-huBrE3 resulted in large breast tumor destruction without toxicities. The stem cell support used in his Phase l RIT trial allows further dose escalation and possible large percentage of responses given the lack of toxicity and potent tumoricidal effect of the initial low doses of (90) Y-huBrE3 administered to date. Concomitant or subsequent RIT with another anti-breast cancer antibody, huMc3, should be tested, considering the results with (90)Y-huBrE3. Developing the selective RIT employing two distinct breast antigens could provide synergistic reagents able to overcome tumor cell heterogeneity, problems of antibody penetration and eventually provide an adequate non-toxic treatment and possible eventual cure for metastatic breast cancer.