Tumor targeting puts very high demands on antibodies with respect to affinity, specificity but also stability of the protein. Recent advances in the design of fully synthetic antibody libraries (1) make it now possible to obtain such antibodies. Using in vitro selection and evolution tools such as ribosome display (2, 3, 4, 5, 6), it has been possible to select and further improve antibodies by directed evolution totally in vitro, without the use of any cells. Picomolar affinities have been routinely obtained (3, 4, 5, 6), and very high selectivity even to targets that are totally non-immunogenic, such as the telomeric DNA.
Using an antibody against EpCAM as a model system (7, 8, 9), the application of these technologies to tumor targeting will be discussed. An optimization of stability, valency and molecular weight has been carried out. Recently, the information gathered from directed evolution could be used in structured based engineering to complement directed evolution. Recent results on tumor targeting with these molecules will be discussed.
This abstract was published in Cancer Immunity, a Cancer Research Institute journal that ceased publication in 2013 and is now provided online in association with Cancer Immunology Research.
- Copyright © 2003 by Robert D. Schreiber