Recombinant antibodies, which are also called genetically engineered antibodies, have emerged as an innovative technology with applications in research, diagnosis, and therapy. This article provides a general background to recombinant antibodies and an overview of their applications, potential benefits, and limitations.
Recombinant vs traditional antibodies: what is the difference?
The key differences between traditional and recombinant antibodies are the production method and the antibodies’ resulting properties.
In traditional antibody production, researchers immunize animals with the target antigen to stimulate antibody production. Antibodies are then harvested from the animal’s blood or serum and purified.
Recombinant antibodies are produced in vitro rather than by infecting living organisms. The technology typically involves obtaining antibody genes from source cells including hybridomas and phage display libraries, amplifying and cloning the genes into an expression vector, introducing the vector into a host (bacteria, yeast, or mammalian cell lines), and achieving adequate expression of the functional antibody.1,2
Recombinant antibodies have advantages over traditional antibodies that can improve their quality in specific applications.
Optionally, manufacturers can engineer the recombinant antibodies to have specific properties, such as higher binding affinity, improved stability, or the ability to target particular cell types (which is not possible with traditional antibodies).
Applications of recombinant antibodies
Recombinant antibodies are a fast-growing class of biopharmaceutical products with many therapeutic applications. For example, the anti-HER2 antibody trastuzumab has been used to treat HER2-positive breast cancer. Another example is the anti-EGFR antibody cetuximab, which is effective against colorectal and head and neck cancer.3,4
In the biotechnology industry, scientists use recombinant antibodies to study protein structures and signal transduction pathways. For example, Oregon Health & Science University researchers have used recombinant antibodies to study the structure and function of the human serotonin transporter.5
Recombinant antibodies can also be applied to detect foodborne pathogens, toxins, antibiotics, pesticides, and mycotoxins in food.6
Precise design, efficient production, and ethical advantages
The ability to precisely design and engineer recombinant antibodies with desired properties, such as increased affinity, specificity, and stability, makes them more versatile and valuable in different applications.
Manufacturers can produce recombinant antibodies in large quantities and with consistent quality, making them suitable for commercial production. In addition, laboratories can produce an antigen-specific recombinant antibody in as few as eight weeks. This compares favorably to historical timelines of four months to produce an antibody using immunization processes. The production of recombinant antibodies is highly reproducible since it relies on a known and defined DNA sequence. Moreover, recombinant antibodies are genetically stable. Unlike traditional antibody production, they do not exhibit genetic drift, antibody expression variation, and antibody sequence mutation that can cause non-specific binding.
The high cost of recombinant antibodies: a barrier to accessibility
Recombinant antibodies have advantages over traditional antibodies that can improve their quality in specific applications. But making high-quality antibodies requires skilled labor and increased manufacturing costs.
The key differences between traditional and recombinant antibodies are the production method and the antibodies' resulting properties.
The high cost can make recombinant antibody-based therapies inaccessible to many patients who need them. For instance, in Canada, trastuzumab costs $49,915 and $28,350 per patient treated in the adjuvant and metastatic breast cancer settings, respectively.7 This corresponds to an average increase in healthcare expenditure of approximately 19 percent over conventional management without recombinant antibodies.
Recombinant antibodies represent a powerful technology with increasing applications. As the field evolves, researchers and industry professionals will explore new ways to optimize and use this technology. We can expect new and transformative discoveries that will shape the fields of science and medicine.
1. “Hybridoma technology; advancements, clinical significance, and future aspects”. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521504/.
2. “Recombinant antibodies for diagnostics and therapy against pathogens and toxins generated by phage display”. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168043/
3. “Trastuzumab for early-stage, HER2-postive breast cancer: a meta-analysis of 13 864 women in seven randomised trials”. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00288-6/fulltext.
4. “Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck”. https://www.nejm.org/doi/full/10.1056/nejmoa053422.
5. “X-ray structures and mechanism of the human serotonin receptor”. https://www.nature.com/articles/nature17629.
6. “Recombinant antibodies and their use for food immunoanalysis”. https://link.springer.com/article/10.1007/s00216-021-03619-7.
7. “The cost burden of trastuzumab and bevacizumab therapy for solid tumours in Canada”. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442764/.