What are the benefits of using recombinant antibodies?

Recombinant antibodies have become one of the most successful biological reagents for many applications. In a nutshell, they are monoclonal antibodies produced in recombinant expression systems such as bacterial, yeast, insect, plant, or mammalian cells. These cell lines are extremely versatile, allowing the production of antibodies in animal-free media (i.e. serum) and a fast scale-up of production without sacrificing yield and purity.

Therapeutic antibodies and many diagnostic antibodies (those integrated into medical devices or used for in vitro diagnostics) are typically produced in recombinant expression systems. However, research antibodies are still only sparsely produced using recombinant technologies and many are still natively produced in hybridomas.

Recent studies have shown that native production in hybridomas may be hindering the standardization of these reagents. Many hybridoma cell lines are prone to genetic drift often resulting in the irreversible loss of antibody-encoding genes. Other studies have also shown that some hybridomas may carry additional light or heavy chains, resulting in a lower purity of the resulting monoclonal antibodies.

For these reasons, many experts are urging us to adopt recombinant antibodies in research as they bypass the most important pitfalls of monoclonal antibody production. The most important benefits of using recombinant antibodies in research, therapy, and diagnostics include:

• Higher and more consistent production yields – recombinant expression systems are continuously being engineered and optimized for antibody production, in this way, most commercially available cell lines can achieve high antibody titers with little optimization.
• Higher purity – many hybridoma cell lines grow very poorly in chemically defined medium and often require animal serum for growth. Since serum contains IgG, these unspecific immunoglobulins are known to reduce the purity of hybridoma-produced monoclonal antibodies. This limitation is easily overcome by recombinant production in high-yield expression systems.
• Standardization of antibody reagents – experts have pointed out the lack of antibody characterization and validation (in specific applications) as the main reason for inconsistent results in research. In this case, the shift towards recombinant antibodies is expected to help overcome that limitation. Since the sequences of recombinant antibodies are readily available, they are more readily characterized
• Protection of antibody sequences – recombinant production requires that the sequence of a specific antibody is known, for this reason, it is easier to store the information and to protect it if desired.
• Easier to manipulate – since antibody sequences need to be known for the production of recombinant antibodies, this makes it easier to manipulate these molecules. By analyzing the sequence in silico, it is straightforward to engineer these antibodies via in vitro affinity maturation, bispecific antibody development, antibody-drug conjugate development, among others. Moreover, monoclonal antibodies can only be produced as full-length immunoglobulins, while recombinant antibodies can be produced in a multitude of formats: scFv, Fab, Fc-protein conjugates, among others.
• Animal-free production – native production of antibodies in hybridomas is often dependent on animal use (ascites) as some of these cell lines grow very poorly in defined and serum-free growth media. In contrast, recombinant cell lines are fully adapted to growing in a defined medium lacking animal serum.
• Wide variety of commercial solutions – as the field continues to push towards standardization, many commercial solutions for transient expression of antibodies have become available. These expression kits are making recombinant antibody production more accessible especially for research applications.

The use of recombinant antibody production processes presents many advantages. These antibodies can easily overcome the most common pitfalls of monoclonal antibody production. Moreover, they are expected to minimize inconsistencies in immunoassays and allow a greater level of standardization in this field.