Advantages of monoclonal antibodies (mAbs) as biopharmaceuticals are big and numerous, as is evident by the hundreds of mAb-based therapeutics currently in clinical trials. Practically every biopharmaceutical company worth its salt invests in antibody technology in some manner, hence valuing its huge potential and merit.
Key properties of mAbs are their high selectivities, specificities and affinities that can be optimized towards nearly every biomolecule of interest. Moreover, their recombinant engineering and production in mammalian cell lines maximizes their batch-to-batch quality, purity and immunologic compatibility with patients.
Let’s have a look at their advantageous properties in depth.
Since the development of hybridoma technology by Georges Köler and Cesar Milstein in 1975, monoclonal antibodies have been extremely successful in many fields of life sciences, sparking a billion dollar industry, and the two researchers were awarded the Nobel Prize in physiology/medicine in 1984.1
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The generation of hybridoma cells from single B lymphocytes (B cells) and myeloma cells leads to cell lines that secrete poly-peptides termed immunoglobulins with high binding selectivity to a single epitope on their target antigen, enabling previously unfeasible applications. Moving away from immunizing and bleeding animals to isolate antibodies with high cross-reactivity towards continuous culture of cell clones in vitro and in the ascites technique was a massive step forward for biotechnology.
This breakthrough allowed the development of immunoassays, immunotherapies and monoclonal antibody treatments. Additionally, they sparked innovation in research and medicine.
Some of the most significant advantages of monoclonal antibodies include
The hitherto unknown specificity and low variability of monoclonal antibodies allows the reliable detection of miniscule differences between biomolecules. This unique property allowed the development of reagents for assays to e.g. quantify biomarker candidates for pathologies (e.g. in SARS-COV-2 antigen test kits) and make predictions regarding disease severity and susceptibility to certain therapeutic options.
These tests are often realized in the form of flow cytometry, immuno-blotting, and enzyme-linked immunosorbent assay (ELISA), which offer unprecedented possibilities to perform research experiments.
MAbs have been continually revolutionizing medicine for several decades. Since mAbs correlate to certain types of antibodies, key players in the human immune system, monoclonal antibody therapies are able to stimulate disease-fighting activation of immune responses and modulate certain signaling pathways of immune cells. They can be engineered to selectively fight cancer cells or infectious diseases for which no vaccinations are available and are very successfully used against autoimmune diseases.
Additionally, mAb therapeutics show relatively benign side effects compared to traditional chemotherapeutics, but administration in a healthcare center and monitoring of vital parameters such as heart rate and blood pressure is generally required by the FDA.
Polyclonal antibodies were the first format of antibodies that was used in the fledgeling life-sciences. They were harvested from the blood of animals that were injected with an antigen of interest. The animals’ immune system would generate a plethora of antibodies against this specific antigen, but without selectivity to a single epitope on its surface. Polyclonal antibodies can be considered a diverse mixture of antibodies.
Nonetheless, they offer several advantages:
polyclonal antibodies mAbs relatively easy to produce skilled and trained workers required no modern molecular biology laboratory required fully equipped laboratory needed relatively quick production few weeks lead time broader affinity distribution desirable in some applications single-epitope selectivity, sharp affinity distribution
As always, the unique restraints of each project define the ideal antibody format.
Recombinant monoclonal antibodies are the next step in the evolution of antibodies. Using recombinant technologies, they can be designed at the drawing board on the genetic level and then optimized and engineered in the laboratory. Large scale production of recombinant antibodies can be performed in mammalian cell culture using Chinese Hamster Ovary (CHO) cell lines.
They offer several key advantages over mAbs:
What is a monoclonal antibody?
Monoclonal Antibody production
Application of monoclonal antibodies
Recombinant antibody production service
1.KÖHLER G, MILSTEIN C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. Published online August 1975:495-497. doi:10.1038/256495a0