immunoadhesin combines the framework sequences from a human mAb with sequences from a human protein that carries a target-recognition function. The most common example of this type of fusion protein combines the hinge and Fc regions of an immunoglobulin (Ig) whith domains of a cell-surface receptor that recognizes a specific ligand. This type of molecule is called an “immunoadhesin” because it combines “immune” and “adhesion” functions. Other names used are “Ig-chimera”, or “Ig” or “Fc-fusion protein” or “receptor globulin”. In a typical immunoadhesin, the variable regions of the antibody molecule are replaced by the ligand binding region of a receptor while the antibody Fc region is retained. Depending on the Ig isotype, the Fc region can confer a long half-life in the circulatory system, as well as confer immune effector functions. In addition, the hinge region is retained to provide conformational flexibility that can allow the Fc and receptor regions to funciton independently. (Charnow Trends Biotechnol 14, 1996, 52-60). Exemplary antibody-immunoadhesin chimeras are the bispecific CD4-IgG chimeras described in Berg PNAS (USA) 88; 4723-4727 (1991) and Chamow, J. Immunol. 153:4268 (1994).
Types of Immunoadhesin Structures
Cleavable immunoadhesins: Like antibodies, immunoadhesins can be cleaved enzymatically at the hinge to release the fusion partner. In some cases, the fusion partner itself may contain sequences that are susceptible to cleavage by papain which is a protease. Sequences which are recognized by more selective proteases such as thrombin have also been introduced into the hinge region of immunoadhesins. See Charnow above.