Bispecific antibodies and their applications.pdf

REVIEW Open Access Bispecific antibodies and their applications Gaowei Fan1,2, Zujian Wang3, Mingju Hao1,2 and Jinming Li1,2* Abstract Bispecific antibodies (BsAbs) recognize two different epitopes. This dual specificity opens up a wide range of applications, including redirecting T cells to tumor cells, blocking two different signaling pathways simultaneously, dual targeting of different disease mediators, and delivering payloads to targeted sites. The approval of catumaxomab (anti-EpCAM and anti-CD3) and blinatumomab (anti-CD19 and anti-CD3) has become a major milestone in the development of bsAbs. Currently, more than 60 different bsAb formats exist, some of them making their way into the clinical pipeline. This review summarizes diverse formats of bsAbs and their clinical applications and sheds light on strategies to optimize the design of bsAbs. Keywords: Bispecific antibody, BiTE, Cancer, Formats, Catumaxomab, Diagnosis Background Currently, 44 monoclonal antibody (mAb)-based prod- ucts are marketed, which generated approximately $75 billion USD in total worldwide sales in 2013 [1]. Thera- peutic antibodies have become a mainstay of therapeutic options for patients with cancer and autoimmune, in- flammatory, and various other diseases [2, 3]. However, mAbs have several limitations. Patients receiving mAb therapy may develop drug resistance or fail to respond to treatment [4]. Cancer and other diseases are multifac- torial, with many signaling pathways implicated in pathogenesis. Single-target immunotherapy does not seem to destroy cancer cells sufficiently. Bispecific anti- bodies (BsAbs) have been posited as potential cancer therapeutic agents for decades but have only recently begun to bear fruit. BsAbs show several advantages [5]: (1) bsAbs can redirect specific immune cells to the tumor cells to enhance tumor killing, (2) bsAbs will enable the simultaneous blocking of two different mediators/ pathways that exert unique or overlapping functions in pathogene