Abstract
With the current biotherapeutic market dominated by antibody molecules, bispecific antibodies represent a key component of the next-generation of antibody therapy. Bispecific antibodies can target two different antigens at the same time, such as simultaneously binding tumor cell receptors and recruiting cytotoxic immune cells. Structural diversity has been fast-growing in the bispecific antibody field, creating a plethora of novel bispecific antibody scaffolds, which provide great functional variety. Two common formats of bispecific antibodies on the market are the single-chain variable fragment (scFv)-based (no Fc fragment) antibody and the full-length IgG-like asymmetric antibody. Unlike the conventional monoclonal antibodies, great production challenges with respect to the quantity, quality, and stability of bispecific antibodies have hampered their wider clinical application and acceptance. In this review, we focus on these two major bispecific types and describe recent advances in the design, production, and quality of these molecules, which will enable this important class of biologics to reach their therapeutic potential.
Highlights
Over recent decades, immunotherapies, including checkpoint inhibitors, adoptive cell transfer, monoclonal antibodies, and vaccine treatments, have become efficient and highly specific treatments to fight cancer by boosting a patient’s immune system
Both dual-affinity re-targeting proteins (DARTs) and bispecific T-cell engager there are three (BiTE) molecules were derived from the same parental antibodies, with DART molecules performing better in maximal B-cell lysis, requiring less concentration for half-maximal B-cell lysis, and in molecular markers of T-cell activation [40]
Two Tandem diabodies (TandAbs) format drugs are in clinical trials—AFM13 (CD30xCD16) for natural killer (NK) cell recruitment and AFM11 (CD19xCD3) for T-cell recruitment [51]
Summary
Immunotherapies, including checkpoint inhibitors, adoptive cell transfer, monoclonal antibodies, and vaccine treatments, have become efficient and highly specific treatments to fight cancer by boosting a patient’s immune system. Through three decades of development and exploration, therapeutic monoclonal antibodies have become the most widely used and approved immunotherapy method in clinical practice to treat various malignant tumors [1] These antibodies are designed to bind to specific targets found on cancer cells and destroy them by activating the patient’s immune system. Bispecific antibodies can target two different antigens at the same time [5], such as simultaneously binding tumor cell receptors and recruiting cytotoxic immune cells This enhanced functionality may potentially result in fewer side effects and fewer injections. Advanced design strategies around phage display screening, antibody conventional monoclonal antibodies, great [25], production challengestechnology with respect to the quantity, quality, linker engineering, quadroma technology knobs-into-holes [26], common light chain and stability of bispecific antibodies have hampered their wider clinical application and acceptance [27], CrossMAb technology [28], and protein engineering have all been extensively investigated, [24]. Focus on the design and manufacture of these two major bispecific molecule types and describe the recent developments in the therapeutic potential and opportunities in bispecific antibody production
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