Bispecific antibodies: design, therapy, perspectives

Sedykh, Sergey E; Prinz, Victor V; Buneva, Valentina N; Nevinsky, Georgy A

sAbs compared to combination therapy with two monospecific drugs makes it possible to optimize expenses by reducing the cost of development and clinical trials. Since one disease modulator may play an essential role in several independent pathways and coexpression of different receptors has been found in many tumors, targeting of two different growth-promoting receptors on a single tumor cell may increase the antiproliferative effect and help to avoid the development of resistance. 13, 14 The sales of more than 50 mAbs presented on the pharmaceutical market have reached more than US$60 billion per year. According to a 2014 estimation, the market of therapeutic BsAbs will grow up to $5.8 billion per year by 2024. 15 Therapeutic BsAbs approved for medical use are directed for the treatment of "liquid" tumors: blood cancer (leukemia and lymphoma). The specialty of "liquid tumors" is that palpable tumors that can be mechanically probed do not form in the body, unlike solid tumors (breast, uterus, rectum). Leukemia and lymphoma never develop symptoms typical of other oncological pathologies, since malignant leukocytes proliferate in the bone marrow and come into the bloodstream as individual cells, making them available for BsAb therapy. There are other diseases for which BsAbs are being developed: autoimmune (arthritis, asthma, diabetes), infectious (pneumonia), hemophilia, and Alzheimer's disease. 6