Many therapeutic targets are
cell surface receptors, which can be challenging
antigens for antibody generation. For many therapeutic applications, one needs
antibodies that not only bind the
cell surface receptor but also are internalized into the cell. This allows use of the antibody to deliver various payloads into the cell to achieve a
therapeutic effect. Phage antibody technology has proven a powerful tool for the generation and optimization of human
antibodies to any
antigen. While applied to the generation of
antibodies to purified
proteins, it is possible to directly select cell binding and internalizing
antibodies on cells. Potential advantages of this approach include:
cell surface receptors are in native conformation on intact cells while this might not be so for
recombinant proteins;
antibodies can be selected for both cell binding and internalization properties; the
antibodies can be used to identify their
tumor associated
antigens; and such
antibodies can be used for human treatment directly since they are human in sequence. This review will discuss the factors that impact the successful selection of cell binding and internalizing
antibodies. These factors include the cell types used for selection, the impact of different phage antibody library formats, and the specific selection protocols used.