In evaluating the immunogenic potential of antibody sequences, we find it useful to characterize those antibodies according to two separate criteria; namely Tregitope content and effector, or neo-epitope, content. Antibodies with low neo-epitope content and high Tregitope content are the least likely to be immunogenic. Antibodies with low neo-epitope content and low Tregitope content are also frequently non-immunogenic. Antibodies in this category frequently produce anti-therapeutic antibody response rates between 5% and 10%. Antibodies with high neo-epitope content and high Tregitope content are the most difficult to characterize. In some cases, the immunogenic potential of neo-epitopes contained in humanized antibodies can be effectively controlled in the presence of significant numbers of Tregitopes. However, in general, we expect antibodies in this category to be more immunogenic than antibodies with fewer neo-epitopes and/or more Tregitopes. Antibodies with high neo-epitope content and low Tregitope content tend to be the most immunogenic with immunogenicity rates frequently exceeding 10%. Most chimeric antibodies fall into this category.

Additional factors not analyzed here, such as dose, route, purity, aggregation, mechanism of synthesis (i.e. mammalian vs. bacterial expression), and target can also affect observed anti-therapeutic antibody response.