Bispecific antibodies for cancer therapy: A review

The ability to produce monoclonal antibodies with defined and distinct specificities has resulted in a vast spectrum of therapeutic monoclonal antibodies including bispecific antibodies (BsAbs). Several types of BsAbs have been produced but the most well-known of these are trispecific antibodies (TrAbs or TrioMabs) and bispecific T cell engager antibodies (BiTE). TrAbs have two variable segments for antigen binding and an Fc component to recruit immune cells. Catumaxomab is a TrAb that has orphan drug status from the Food and Drug Administration (FDA) for EpCam positive gastric and ovarian tumors and was previously approved by the European Medicinal Agency (EMA) for the same indication. One arm of catumaxomab binds to EpCAM, the other binds to CD3 on T cells and the Fc portion recruits immune cells. Catumaxomab is no longer being produced by the manufacturer due to logistic considerations and hence not available in the European market. Blinatumomab is a BiTE that comprises of two variable segments only with one arm binding to CD19 and the other binding to CD3. Blinatumomab has been approved for relapsed or refractory B-cell precursor ALL in adults and children by the FDA. There are over 50 bispecific antibodies currently on clinical trials for various malignancies and the hope is that in the future many of these, with better understanding of principles and techniques of production, will provide treatment options for many different types of cancer.