Cancer Immunity 3 Suppl. 1:2 (2003)

Improving antibodies by evolution and engineering

Robert D. Schreiber^1*, Hiroaki Ikeda¹, Allen Bruce¹, Pilar Gil¹, Gavin Dunn¹, Kathleen Sheehan¹, Vijay Shankaran¹, and Lloyd J. Old²

¹Washington University, School of Medicine, St. Louis, MO
²Ludwig Institute for Cancer Research, New York, NY
^*Presenting author

Abstract

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.

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