Immunogenicity of therapeutic proteins

The use of therapeutic proteins originates in the 19th century, when polyclonal horse antitetanus and antidiphtheria immunoglobulins were used for the first time. Then in the 1920s, bovine insulin and porcine insulin were introduced for the treatment of diabetes. Since then, insulin and many more protein drugs, including growth factor, erythropoietin, and a whole range of monoclonal antibodies, have become major therapeutic drugs. Currently, a substantial portion of newly approved drugs is constituted by therapeutic proteins. A common feature of all therapeutic proteins is their immunogenicity, the potential to evoke an adverse immune response. In the field of protein drugs, the presence of antidrug antibodies (ADAs) is often referred to as seroprevalence, whereas the term “immunogenicity” is referred to as a quantitative measurement of ADA titers (Sominada et al., 2007). However, this distinction is not a general rule. Therefore, in this chapter the term “immunogenicity” will be used in a general manner, describing the potential of the therapeutic protein to evoke an adverse immune response.