Strategies for the Generation of Bispecific Antibodies

Bispecific antibodies (BsAbs) are engineered immunoglobulins that can simultaneously recognize two distinct antigens or two distinct epitopes on the same antigen. They exhibit cooperative therapeutic effects surpassing those of natural monoclonal antibodies, such as bridging the immune cells and tumor cells to stimulate targeted immune response, or blocking codependent signaling pathways. These advantages make them attractive therapeutic reagents for various diseases such as cancers, immunodeficiency syndromes, and ophthalmic disorders. However, the unique structural characteristics of BsAbs pose various challenges to their preparation. In the past few decades, various types of BsAbs have been designed and prepared through genetic engineering or chemical conjugation strategies, many of which have been approved as drugs or entered clinical trials. This review provides a systematic summary of these strategies and their corresponding principles, and focuses on the application of modern genetic engineering and chemical conjugation methods in the generation of BsAbs.