Antibody Engineering for Pursuing a Healthier Future

Saeed, Abdullah F. U. H.; Wang, Rongzhi; Ling, Sumei; Wang, Shihua

The tumor necrosis factor (TNF) and interleukins 1 and 6 (IL-1 and IL-6) proinflammatory cytokines cause multifactorial disease such as cancer and systemic inflammations. Moreover, these factors are involved in redundancy of disease-mediation and crosstalk between signal cascades (Arango Duque and Descoteaux, 2014). Similarly, upregulation of alternative receptors and pathway switching is often related to resistance to therapy (Dong et al., 2011) . The obstruction of several targets or multiple sites on one target is associated with improved therapeutic efficacy. Over the past decade, dual targeting with bispecific antibodies has gradually switched to combinatorial or cocktail therapy. This targeting technique is based on the targeting of multiple disease-modifying reagents with one drug. Several bispecific molecules such as diabodies, IgG-like tetravalent Di-diabodies, IgG-scFv fusion proteins, and bispecific Adnectins TM have been developed to target tumor mediated receptors such as members of the epidermal growth factor (EGF) receptor family, i.e., EGFR, HER2, HER3, and HER4,45 and the insulin-like growth factor 1 receptor (IGF-1R; Tao et al., 2007; Kontermann and Brinkmann, 2015) . The application of a single, bispecific molecule is advantageous because it is less complicated to administer to patients, requires reduced preclinical and clinical testing, and has cost effective manufacturing (Kontermann and Brinkmann, 2015) .