Bioengineering of Antibody Fragments: Challenges and Opportunities

Abstract

Antibody fragments are used in the clinic as important therapeutic proteins for treatment of indications where better tissue penetration and less immunogenic molecules are needed. Several expression platforms have been employed for the production of these recombinant proteins, from which E. coli and CHO cell-based systems have emerged as the most promising hosts for higher expression. Because antibody fragments such as Fabs and scFvs are smaller than traditional antibody structures and do not require specific patterns of glycosylation decoration for therapeutic efficacy, it is possible to express them in systems with reduced post-translational modification capacity and high expression yield, for example, in plant and insect cell-based systems. In this review, we describe different bioengineering technologies along with their opportunities and difficulties to manufacture antibody fragments with consideration of stability, efficacy and safety for humans. There is still potential for a new production technology with a view of being simple, fast and cost-effective while maintaining the stability and efficacy of biotherapeutic fragments.

Utilizing fab fragment‐conjugated surface plasmon resonance‐based biosensor for detection of SalmonellaEnteritidis

“…46 The use of smaller-sized antibody fragments, such as Fab and scFv fragments, allows a higher density of target binding to be achieved in a given volume. 47 Antibody fragments can be produced by various genetic modifications or chemical reduction methods. Recombinant antibodies used for this purpose are attractive due to their high specificity, purity, and homogeneity.…”

“…Consequently, the utilization of antibody fragments as bioreceptors, as opposed to full‐length antibodies, can result in noticeable signal amplification 46 . The use of smaller‐sized antibody fragments, such as Fab and scFv fragments, allows a higher density of target binding to be achieved in a given volume 47 . Antibody fragments can be produced by various genetic modifications or chemical reduction methods.…”

Development of an antibody-ligand fusion protein scFvCD16A-sc4-1BBL in Komagataella phaffii with stimulatory activity for Natural Killer cells

“…In recent years, approximately 80% of recombinant therapeutic proteins have been expressed in mammalian expression system [47]. But the microbial system, especially yeast system, can be an alternative to produce pharmaceutical protein with improved folding machinery and less cost [52][53][54]. In this study, we employed K. phaffii as the expression production host, successfully expressed the antibody-ligand recombinant protein (Fig.…”

Charting the Course in Sequencing Antibody-Drug Conjugates in Breast Cancer

“…As mentioned earlier, antibodies adopted in clinical practice as therapeutic proteins owe their success to effective tissue penetration and a reduced incidence of immunological reactions [ 10 ]. To enable antibody production, Escherichia coli and Chinese hamster ovary (CHO) cell-based systems are the most promising hosts due to their higher expansion capabilities.…”