Abstract
Bispecific antibodies, which possess two distinct specificities, are primarily produced through genetic engineering. They are often used in cancer therapy, and strategies for cross-linking cancer cells and T cells have been studied extensively for a long time. Bispecific antibodies are categorized as either natural IgG-type or non-natural, and various technologies have contributed to the uniform production of both types. Small bispecific antibodies are expected to be produced using a cost-effective bacterial expression system and to effectively permeate solid tumors. Here, we first outline the development history and commercialized examples of natural IgG-type and non-natural bispecific antibodies as pharmaceuticals. Then, we will introduce the development of small bispecific antibodies and the multifaceted progress we have made in enhancing their functionality.