Factors involved in the immunogenicity of biopharmaceutical products and mitigation strategies

During the past decades, there has been a dramatic increase in the demand for biopharmaceutical products. Despite the great potential of these products in providing life-saving medications for patients, the clinical application of several protein-based therapeutics has been weakened due to the development of un-intended immune responses against the proteins, compromising their safety and effectiveness. Patients may develop persistent immune responses against protein-based therapeutic agents due to the formation of neutralizing antibodies. Therefore, the immuno-genic potential of such agents remains a major safety concern for their therapeutic application. While it is known that product-and host-related factors affect immune responses, there is less information about other factors involved in the induction of such immune responses. This review aimed to provide an overview of the immunogenicity of protein-based therapeutics and explains the immune mechanisms and factors that affect immunogenicity, immunogenicity effects, preclinical screening techniques, as well as the methods used to mitigate immunogenicity.