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Novel radiolabeled antibody conjugates

Abstract

This article reviews the development of radioimmunoconjugates as a new class of cancer therapeutics. Numerous conjugates involving different antigen targets, antibody forms, radionuclides and methods of radiochemistry have been studied in the half-century since radioactive antibodies were first used in model systems to selectively target radiation to tumors. Whereas directly conjugated antibodies, fragments and subfragments have shown promise preclinically, the same approaches have not gained success in patients except in radiosensitive hematological neoplasms, or in settings involving minimal or locoregional disease. The separation of tumor targeting from the delivery of the therapeutic radionuclide in a multistep process called pretargeting has the potential to overcome many of the limitations of conventional, or one-step, radioimmunotherapy, with initial preclinical and clinical data showing increased sensitivity, specificity and higher radiation doses delivered. Our particular focus in pretargeting is the use of bispecific, trimeric (three Fab′s) constructs made by a new antibody engineering method termed ‘dock-and-lock.’

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Acknowledgements

We thank Professor J-F Chatal and Dr J Barbet of Nantes for participating in many studies conducted with our pretargeting agents; Drs C-H Chang, E Rossi and W McBride of Immunomedics and IBC Pharmaceuticals for reagent and technology development; Drs SM Larson and P Zanzonico of Memorial Sloan-Kettering Cancer Center and Drs S Goldsmith and S Vallabhajosula of Weill Medical College of Cornell University, for collaboration in microPET studies; and Dr H Karacay for conducting many of the preclinical studies reported herein. This work has been supported in part by P01 CA103985, NJDHSS 06-1853-FS-N0 and CDG-06103.

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Correspondence to D M Goldenberg.

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Goldenberg, D., Sharkey, R. Novel radiolabeled antibody conjugates. Oncogene 26, 3734–3744 (2007). https://doi.org/10.1038/sj.onc.1210373

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