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.
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| Peterson, J A; Blank, E W; Ceriani, R L (1997) Effect of multiple, repeated doses of radioimmunotherapy on target antigen expression (breast MUC-1 mucin) in breast carcinomas. Cancer Res 57:1103-8 |
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