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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA062352-05
Application #
6127855
Study Section
Special Emphasis Panel (ZRG1-ET-2 (01))
Program Officer
Wu, Roy S
Project Start
1994-08-12
Project End
2003-04-30
Budget Start
2000-05-18
Budget End
2001-04-30
Support Year
5
Fiscal Year
2000
Total Cost
$308,048
Indirect Cost
Name
Cancer Research Fund of Contra Costa
Department
Type
DUNS #
City
Walnut Creek
State
CA
Country
United States
Zip Code
94598
Johnson, Timothy K; Cole, William; Quaife, Robert A et al. (2002) Biokinetics of yttrium-90--labeled huBrE-3 monoclonal antibody. Cancer 94:1240-8
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
Speck, R R; Couto, J R; Godwin, S G et al. (1996) Inverted Fab2s (IFab2s): engineering and expression of novel, dimeric molecules, with a molecular weight of 100 000. Mol Immunol 33:1095-102