Molecular imaging of cancer has the potential to facilitate early detection and to provide a more detailed assessment of disease and tumor margin. Molecular imaging probes have been heralded by the FDA Critical Path Initiative as tools to increase the speed and cost-effectiveness of clinical trials for cancer therapies. However, imaging probes currently in use in the clinic are limited by a lack of specificity and/or sensitivity or are limited to a small subset of cancers. Therefore, new molecular imaging probes with more broad applications to cancer are needed.
UCSF investigators have developed novel antibodies to two human antigens that are highly expressed on tumor cells. Matriptase (MT-SP1) is a serine protease that is often upregulated in epithelial cancers including breast, colon and prostate cancers. Matriptase expression has been correlated with cancer stage and subtype. Antibody A11 is specific, fully human antibody that binds to the active form of matriptase. Animal model testing has revealed no side effects in adult control mice and has shown utility of A11 in in vivo tumor imaging, phage display, and immunohistochemistry. Testing of the IgG form of A11 in mouse xenograft model of breast cancer and colon cancer showed localization to the xenograft tumors and high tumor/background contrast in mice with matriptase-positive tumors, but not matriptase-negative tumors.
UCSF inventors have also developed two uniqe fully human Fab and IgG antibody inhibitors of urokinase plasminogen activator receopt (uPAR). uPAR-mediated signaling is associated with invasion, survival and metastasis of tumor cells, including those from primary breast and lung cancers. Attachment of fluorophores, radionuclides, or paramagnetic contrast agents allow use in tumor visualization, as demonstrated in animal models of cnacer. The antibodies show no reactivity to mouse uPAR and are selecttive for uPAR-positive human cells in mouse xenograft models, enabling the use of these antibodies as research tools. These anti-uPAR antibodies show great promise as diagnostic and prognostic agents and studies are under way to examine their utility in grading human tumors for evaluatin of disease stage.
|United States Of America||Issued Patent||9,029,509||05/12/2015||2010-063|
Additional Patent Pending