Risk-based approach of bioanalytical methods for clinical immunogenicity assessment of multidomain biotherapeutics

Antibody engineering has dramatically evolved in recent years, resulting in current conventional antibody therapeutics having fewer immune-related adverse effects observed in the clinic. However, the advanced antibody engineering technologies have also created a great variety of novel antibody-based therapeutics with bispecific and multispecific domains entering to the clinic [1]. While having multiple specificities in the same molecule that are capable of binding to multiple different molecular antigens, or two different epitopes on the same antigen, may provide additional efficacy benefit over combination therapy, more bioengineering modifications and complex manufacturing processes are required for multidomain biotherapeutics compared with the conventional monospecific antibody therapeutics. As a result, multidomain biotherapeutics may potentially hold greater risk for immunogenicity and present unique challenges for immunogenicity analysis.