Advances in Bispecific Antibodies Engineering: Novel Concepts for Immunotherapies

Bispecific antibodies are emerging as novel approach for immunotherapies by combining two antigen-recognizing elements into a single construct that is able to simultaneously bind to two distinct targets. Bispecific antibodies can be applied to recruit immunological effector cells for killing of tumor cells or to simultaneously block two signaling pathways or cytokines. Subsequently, they have prompted significant interest for a number of therapeutic applications, both in cancer and in other indications. The growing interest in therapeutic antibodies along with the rapid progress in antibody engineering have yield a multitude of bispecific antibodies formats and derived molecules that differ in size, shape and function. Presently, two major classes of bispecific antibodies are most widely studied: immunoglobulin-like and small single chain Fv (scFv)-based bispecific antibodies. This review summarizes selected key methods used to generate bispecific antibodies, reports new concepts developed for immunotherapy and discusses their potential development and therapeutic benefits.