What if we could train one protein to hunt down just the cells that call illness and leave everything else alone? That’s the science of therapeutic monoclonal antibodies (mAbs). Discovered in 1975 and first approved by the FDA in 1986, these lab-made proteins can now be used to treat cancer, autoimmune disease, and even viral infections.
What are Monoclonal Antibodies?
Monoclonal antibodies (mAb) are proteins that are produced in a laboratory or plant that can act in place of antibodies produced by the human body. They are “monoclonal” because they are single clones, or exact copies, of an antibody, which binds to a single antigen. An individual cell line is developed to produce a specific mAb that will bind to a particular receptor (the antigen).
Scientists begin with a single B-cell that makes an antibody suited for a target antigen, like a tumor marker. By cloning that cell, scientists produce a potentially infinite supply of identical antibodies - all of which are aimed at that target antigen.
Because each mAb is custom-made, side-effects of mAbs are often lower than with broad-spectrum small-molecule drugs.
A Brief History of the Development of Monoclonal Antibodies
- 1975 – Köhler & Milstein invent the hybridoma technique.
- 1986 – Muromonab-CD3 becomes the first FDA-approved therapeutic mAb.
- Today – 100+ mAbs approved, representing 7 of the world’s top-10 selling drugs (FDA, 2024)
A Not-So-Brief History of the Development Monoclonal Antibodies
In 1975, Georges Köhler and César Milstein first described a laboratory method that fuses a single antibody-producing B-cell with an immortal myeloma (cancer) cell. The resulting “hybrid” cell - called a hybridoma - combines the B-cell’s ability to make one highly specific antibody with the myeloma cell’s capacity to divide indefinitely.
Because each hybridoma comes from one original B-cell, every antibody molecule it secretes is identical (monoclonal). Köhler, Milstein, and Niels Jerne would later win the Nobel Prize in Physiology or Medicine in 1984 "for theories concerning the specificity in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies."
Before their win, in 1980 the first FDA-cleared diagnostic test based on a monoclonal antibody (for hepatitis B surface antigen) proved that large-scale production was possible. And, in 1981, clinical trials began for muromonab-CD3 (OKT3), an anti-CD3 antibody that can shut down T-cell activity and potentially treat organ-transplant rejection.
Muromonab-CD3 was approved by the U.S. FDA in 1986 as the first monoclonal antibody ever licensed for human therapy. It was developed to reverse acute rejection in kidney, heart, and liver transplants. Its success not only improved short-term graft survival rates but also validated monoclonal antibodies as a new class of precision drugs.
Why mAbs can work better than small-molecule drugs
Small-molecule drugs excel at many tasks. They’re small enough to slip through cell membranes to switch off enzymes inside the cell. They can be conveniently mass-produced as oral solid dose tablets. They remain cost-effective treatment for chronic illnesses.
The trade-off for them excelling at many tasks is… that they excel at many tasks! Keyword: many. A single small-molecule drug may bind several related proteins, so clinicians must balance desired action against the risk of other interactions within the body.
Monoclonal antibodies, by contrast, are large proteins built to bind to specific, unique regions on an antigen called epitopes. That lock-and-key fit delivers highly-selective performance, which can translate to fewer off-target effects. Their size also keeps them in the bloodstream for a longer period of time, which can reduce dosing and pill burden for patients.
Finally, when mAbs bind to their target, they can trigger antibody-dependent cellular cytotoxicity (ADCC) - bringing an extra layer of immune response to bear against their target antigens.
Therapeutic mAbs, From Lab Bench to Production
Every mAb story starts with a target—a protein or receptor driving disease. How do we produce these amazing molecules on a large scale so we can provide medicine for patients? It all starts with one small vial.
Cell Banks. Once development of a cell line is complete, a master cell bank (MCB) is produced by a GMP laboratory scale production of cells from the final cell line. Each vial of a master cell bank can be used to produce a working cell bank (WCB).
Cell Growth. Starting from a small vial of working cell bank, we end up with a large bioreactor of cells and mAb. As the number of cells (cell mass) increases, the amount of mAb produced by the cell mass increases. Scientists work to maximize cell growth.
Purification of mAbs. Purification uses multiple chromatography and filtration steps to separate the mAb from the cells/cell debris in the bioreactor.
AbbVie’s Therapeutic Monoclonal Antibody Development Expertise
AbbVie Contract Manufacturing offers end-to-end biologics monoclonal antibody manufacturing—from cell-line development to commercial fill-finish—backed by 30+ years of licensed mAb production. Ready to accelerate your Monoclonal Antibodies? Let’s talk .