RADIOIMMUNOTHERAPY OF BREAST CANCER

描述：（申请人摘要）本项目的长期目标是 开发放射免疫治疗（RIT）程序，用于治疗 扩散性乳腺癌患者。具体目标是：1.进行临床 抗乳腺上皮粘蛋白（BEM）抗体对乳腺癌的RIT研究， 人源化BrE 3（huBrE-3）。申请人启动的RIT I期试验， 在干细胞支持下，将继续递增剂量的（90）Y-huBrE-3RIT。 在其结束时，它将为制定第二阶段战略奠定基础。 试验将在随后迅速制定和启动。HuBrE3和 I期和II期的缀合物已经可用， 这是一个非常有经验的RIT中心。2.制备人源化 抗乳凝集素抗体hu-Mc3并启动成像研究。cGMP质量 制备人源化huMc3（15 gm）并与螯合物缀合 用（111）In标记MX-DTPA。类似于申请人的协议已经 将开发使用（111）In-huBrE-3进行的成像试验。到目前为止， huBrE-3已被证明是无毒的，（111）In-huBrB3可能是 最好的乳腺放射免疫成像试剂。这一无可争议的 （90）Y-huBrE3也显示出特异性靶向能力，导致大乳腺癌 无毒性的肿瘤破坏。他在第一阶段使用的干细胞支持物 RIT试验允许进一步的剂量递增和可能的大百分比的 由于缺乏毒性和有效的杀肿瘤作用， 迄今为止施用的初始低剂量的（90）Y-huBrE3。伴随施用或 随后用另一种抗乳腺癌抗体huMc3进行RIT， 测试，考虑到（90）Y-huBrE3的结果。发展选择性RIT 使用两种不同的乳腺抗原可以提供协同试剂， 为了克服肿瘤细胞的异质性、抗体穿透的问题和 最终提供充分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.