Research: Laboratory Program –
R.M. Sharkey, Ph.D.

Dr. Sharkey is the Director of Clinical Research Administration and a Full Member at GSCC. He received his Ph.D. from the University of Kentucky, Lexington, KY in 1982, working with Dr. David Goldenberg on the delivery of cancer therapeutics with antibodies. He has had active funding from the National Cancer Institute and the Department of Energy since 1985.

Dr. Sharkey's current research projects focus on the development of pretargeting methods using bispecific antibodies for applications in cancer imaging and therapy. A pretargeting method is a 2- to 3-step process that first entails the administration of the bispecific antibody. After some time elapses, during which a portion of the bispecific antibody localizes in disseminated tumor sites, while it is cleared from normal tissues, another agent, typically a specially modified peptide, which is carrying a radionuclide or an anti-cancer agent, is given. The bispecific antibody is a protein that is prepared in the laboratory either by recombinant engineering or by simple chemical conjugation. It represents an antibody that has specificity for 2 compounds. One portion of the bispecific antibody is specific for a substance found on tumors. This specificity is responsible for the bispecific antibody's ability to localize to tumors. The other specificity of the bispecific antibody is directed against the peptide. Thus, the bispecific antibody that localizes in the tumor is then able to capture the peptide, which in turn is carrying the imaging or therapeutic agent of interest. Dr. Sharkey's lab is currently evaluating several bispecific antibody pretargeting systems in mouse models and has shown that these methods are highly effective in selectively delivering compounds to cancer. Efforts are presently underway to translate these laboratory findings to a clinical trial that will initially examine the utility of a bispecific antibody pretargeting method to improve the detection of cancer by external imaging. There is also very promising data indicating that this approach may be used successfully for therapy.