Radioimmunotherapy of Tumors: Pretargeting with Bispecific Antibodies
The targeting of radionuclides with antibodies has been a very productive line of investigation for many years. Starting in the middle of the last century at a time before well-defined tumor markers were available, this effort has been at the center of a host of innovations, including the development of monoclonal antibodies, molecularly engineered antibodies and other antibody-related compounds, new procedures for manufacturing radionuclides, and their coupling to antibodies. Progress has led to the approval of two therapeutic agents for select lymphomas, but the therapeutic window is limited by hematological toxicity because the radioactivity bound to an antibody stays in the bloodstream for extended periods. Antibody fragments reduce red marrow exposure, but have not enhanced the therapeutic window sufficiently. An alternative approach known as pretargeting greatly reduces the radioactivity’s residence time in the blood and accelerates the time to maximum tumor accretion while maintaining high tumor uptake. This chapter focuses on the progress being made in using bispecific antibody pretargeting for improved delivery of therapeutic radionuclides.
KeywordsMedullary Thyroid Cancer Bispecific Antibody Hapten System Medullary Thyroid Cancer Patient Human Lymphoma Cell Line
We thank our many colleagues who have contributed to our research efforts in pretargeting, particularly Jacques Barbet, Ph.D., Professor Otto Boerman, Ph.D., Thomas M. Cardillo, Ph.D., Chien-Hsing Chang, Ph.D., Professor Jean-François Chatal, M.D., Ph.D., Habibe Karacay, Ph.D., Professor Françoise Kraeber-Bodéré, M.D., Ph.D., Docent Torsten Liersch, M.D., William J. McBride, Ph.D., Professor Johannes Meller, M.D., and Edmund A. Rossi, Ph.D. The authors have been supported in part by PHS grants P01 CA103985 and R01 CA107088 from the National Institutes of Health.
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