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.
Small Business Information at Submission:
WOOMERA THERAPEUTICS, INC.
115 ETNA ROAD SUITE D LEBANON, NH 03766
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