Chapter 9 - Bispecific antibodies: A promising entrant in cancer immunotherapy

Abstract

Cancer is a dreadful disease and a threat to mankind. With every challenging ailment or illness, there is a need for effective and efficient treatment. Bispecific antibodies (bsAbs), as the name suggests, constitute two paratopes or antigen having distinct specificities, thus can bind two different molecules (or, antigen) simultaneously. bsAbs offer a wide range of applications, for instance, blocking two signaling pathways, redirecting effector immune cells to cancer cells, and delivering payloads (radionuclides, toxic, and immune payloads) to target cells. Bispecific T-cell Engager, an example of a bispecific antibody, represents two antigen-binding fragments, one for T-cell activation and other for effective neutralization of target cells by redirected lysis, thereby bridging the gap between target and effector immune cells. bsAbs can be produced by quadroma technology (by fusing two hybridomas cell lines), chemically coupling of purified antibodies by a disulfide bond succinimidyl-3(2-pyridiylthio)propionate, or by nonreducible thioether bond, each of them is explained in this chapter. In the present section, antibody engineering for affinity maturation and paratope optimization for bsAbs to target various biomarkers such as PD-L1, CTLA-4, HER-2, and CD3 are discussed in detail.