Antibody ABCs: What is Antibody Engineering?

To dive deeper into antibody engineering, take a look at our comprehensive blog post: How Therapeutic Antibodies Are Produced: Antibody Engineering

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Watch the Antibody ABCs video playlist here: https://www.youtube.com/playlist?list=PLM31OdueQLrBKezKpLsLocNHYsfLBaZuE

Antibody engineering is the use of molecular biology techniques to develop antibodies with enhanced or modified properties compared to their naturally occurring counterparts. By engineering antibodies, scientists can improve their affinity, specificity, stability, and other characteristics to better suit a particular application. In the past few years, various engineered antibody drugs have been approved or are in phase II and III clinical trials.¹

In recent years, antibody engineering has fueled the development of next-generation antibody drugs. These advancements are evident in the increasing number of engineered antibody therapeutics that have gained regulatory approval or are progressing through phase II and III clinical trials. These developments reflect the growing demand for more sophisticated and specialized therapeutic antibodies that can target diseases with greater precision and efficacy.

The Evolution of Antibody Formats

As of now, there are many different antibody formats. This began when a methodology was developed to express smaller antibody molecules: Fab and Fv fragments. Various vectors were used with competent Escherichia coli for recombinant antibody construction.² The process involves isolating the antibody genes, inserting them into a bacterial expression vector, and transforming the vector into E. coli cells. Under suitable conditions, the bacteria will produce the desired antibody fragments.

The success of Fab and Fv fragments opened the door to further innovation in antibody design, leading to the development of additional formats like single-chain variable fragments (scFv) and bispecific antibodies. Each of these formats offers distinct benefits. For example, scFvs consist of variable regions from the heavy and light chains of an antibody connected by a short linker, which allows for smaller size and greater tissue penetration.

Bispecific antibodies represent one of the most exciting advances in antibody engineering. These molecules can bind two different antigens simultaneously, which has significant implications for cancer immunotherapy, as they can bring immune cells directly to the tumor cells for more effective destruction.

Related: HTP Recombinant Antibody Production

With the help of antibody engineering, it has now been possible to modify:

• Molecular size

• Pharmacokinetics

• Immunogenicity

• Binding affinity

• Specificity

• Effector function

Fusion proteins of antibodies with various proteins and peptides have yielded targeted biological modifiers, toxins, and imaging agents.

References:

1. H. Saeed, F. U., Wang, R., Ling, S., & Wang, S. (2017). Antibody Engineering for Pursuing a Healthier Future. Frontiers in Microbiology, 8. https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.00495/full

2. Okamoto, T., Mukai, Y., Yoshioka, Y., Shibata, H., Kawamura, M., Yamamoto, Y., Nakagawa, S., Kamada, H., Hayakawa, T., Mayumi, T., & Tsutsumi, Y. (2004). Optimal construction of non-immune scFv phage display libraries from mouse bone marrow and spleen established to select specific scFvs efficiently binding to antigen. Biochemical and Biophysical Research Communications, 323(2), 583-591. https://www.sciencedirect.com/science/article/abs/pii/S0006291X04018741