B-1 cells and naturally occurring antibodies: influencing the immunogenicity of recombinant human therapeutic proteins?

Recombinant human therapeutic proteins are increasingly being used to treat serious and life-threatening diseases like multiple sclerosis, diabetes mellitus, and cancer. An important side effect of these proteins is the development of antidrug antibodies, which can be neutralizing and thus interfere with the efficacy and safety of the drug. Some biophysical properties, for example, aggregation, also can initiate the immunogenic response to human therapeutics. Many other factors including patients' characteristics may influence this response. Besides induced antibodies, autoantibodies (i.e. naturally occurring antibodies [NAs]) against therapeutic relevant proteins in naïve patients are increasingly being identified. The role of autoreactive B cells and their escape from deletion, production of NAs and their pivotal function in the immune system, the dualistic role of B-1 cells in autoimmunity, and the influence of NAs on disease outcome and their possible impact on the efficacy of human therapeutics will be presented and discussed.