MAG-1 Targeting of GRSA on Breast Cancer

DESCRIPTION (provided by applicant): The objective of this project is to utilize different forms of a mouse monoclonal antibody, mMAG-1, not only to direct successful imaging of breast cancer but also to develop more rational approaches to treatment. The hypothesis being tested is that Glycopeptide-Related cell-Surface Antigen (GRSA) will provide a sensitive and reliable target for the detection and effective treatment of breast cancer by mMAG-1 and related antibodies. Our data show GRSA expression is a feature common to all, or most, breast cancers and DCIS. I also shows GRSA-like antigens can be targeted in patients with antibodies, and that our MAG-1 monoAb not only recognizes GRSA in all of breast tumors but also targets GRSA in vitro. Preliminary findings also indicate MAG-1 and 90Yttrium-labeled MAG-1 can decrease growth of breast cancer xenografts in mice. Phase 1 goals are directed towards (i) performing and completing a 'proof of principle' to determine the usefulness of "technetium-labeled Fab fragments of mouse monoclonal antibody (mMAG-1) to successfully image breast cancer tumor xenografts in nu/nu mice, and; (ii) performing and completing a 'proof of principle' determine if MAG-1 (mMAG-1) or 90Yttrium-labeled mMAG-1 can kill or significantly retard the growth of brea tumor xenografts in nu/nu mice. These investigations will employ, RT-PCR, ligation, and cloning, DNA sequencing, immunohistochemistry, antibody modification, Northern and Western analysis with densiometric quantitation, RIA, tumor-directed targeting, whole-body scintigraphy for 99mTechnetium, cytofluorographic and radiometric quantitation, radioligand binding, flow cytometry, and cell and tumor growth assessments. A successful end-point of our Phase 1 studies would be the clear determination that fragments of mMAG-1 can direct radioimaging, and both unlabeled and 90Yttrium-labeled mMAG-1 can kill tumor cells or significantly curtail their growth in vivo. The proposed research is expected to lead to new and successful therapeutic approaches for managing breast cancer.