Moving Towards Recombinant Monoclonal Antibodies
Recombinant Monoclonal Antibodies (rmAbs) are highly reproducible, customizable and pure alternatives to the traditional antibodies produced by hybridomas. Get the antibody protein sequence, either by DNA sequencing or the de novo protein sequencing technology, you can rest assured that you can have the exact antibody made recombinantly anytime in the future.
Monoclonal antibodies (mAbs) are widely used for decades. They are outstanding tools for biomedical research and critical components of many diagnostic tests. Researchers have long used them to track proteins of interest because they bind to specific targets.
Traditionally, monoclonal antibodies are produced by hybridomas. There are many issues related to hybridoma produced antibodies. The first and most important one is contamination. For example, mice used in mAb production may carry several viruses. There are cases that the presence of some of the viruses has been detected in the hybridomas. Therefore, there is no guarantee that the antibody produced is virus-free.
The second issue is the consistency and reproducibility. The hybridoma cell lines can die off, lose their antibody genes, or simply not grow anymore when taken out of the frozen storage. Repeating the process to make another hybridoma using the exact same antigen, will result in a cell line secreting a different monoclonal antibody. This means your original antibody is not reproducible and is lost forever.
The third issue is that hybridoma technology is quite time consuming. This is largely due to the time required for the animals to develop the immune responses after the injection of the antigen. The entire process, from the first injection to scale up antibody production, can take somewhere between 3 to 6 months.
Recombinant antibodies (rAbs) can solve many of the issues. A group of more than 100 scientists highly advocate the use of recombinant antibodies to promote the standardization in research because of the high reproducibility of rAbs (Reproducibility: Standardize antibodies used in research).
Compare to the hybridoma technology, the recombinant antibodies have many benefits.
- High reproducibility. The chemical synthesis process is tightly controlled to achieve ultra low batch-to-batch variability.
- High purity. The recombinant antibodies can be expressed in a chemically defined serum-free mammalian expression system. Thus, it avoids the contamination from serum components and ensure a purity greater than 98%.
- Decreased production time. 6 to 8 weeks v.s. 3 to 6 months.
- Highly customizable. Isotype switching, subtype switching, species switching, reformatting to F(ab’)2, Fab.
- Animal welfare. The recombinant antibody manufacturing process is animal free, thus eliminating the animal welfare concerns as well as all the cost related to animal care.
“To save millions of dollars and dramatically improve reproducibility, protein-binding reagents must be defined by their sequences and produced as recombinant proteins”
Andrew Bradbury, Andreas Plückthun and 110 co-signatories say in Reproducibility: Standardize antibodies used in research.