Recombinant Adenoviruses for In Vivo Expression of Antibody Fragments

A growing number of recombinant antibodies is being developed for immunotherapy of cancer (1 ,2 ) (see also Chapter 2 ). Although these recombinant antibodies can exhibit a potent anti-tumoral activity in vitro, efficacy in vivo is often limited by the short serum half-life of these molecules. Thus, repeated or continuous administrations are required to obtain a sufficiently high serum concentration. An alternative approach to the injection of the therapeutic molecules is the expression and secretion of these proteins in vivo, which leads to high levels of the molecules in the serum (3 –6 ). Furthermore, this approach obviates the need for the preparation of bulk amounts of pure protein. Recombinant adenoviruses are widely used vectors for the delivery of a transgene in gene therapy (7 ). Recently, it was demonstrated that an anti-carcinoembryonic antigen (CEA) scFv-granulocyte/monocyte colony-stimulating factor (GM-CSF) fusion protein is expressed in vivo for a prolonged period of time after intravenous injection of recombinant adenoviruses (8 ).