Monoclonal Antibodies Over Time: What’s Changed?

But monoclonal antibodies can focus just on the cancer cells by recognizing special markers on their surface, leaving normal cells mostly untouched.

However, developing monoclonal antibody treatments hasn’t been easy. Even well-designed versions sometimes caused bad side effects and didn’t work as expected. That meant researchers had to go back and improve the technology.

One major breakthrough that helped make monoclonal antibodies safer and more effective was something called antibody humanization. To understand how that works, it helps to look at the history of how monoclonal antibodies were first developed.

The Origin of Monoclonal Antibodies

The first FDA-approved monoclonal antibody, Orthoclone OKT3® (muromonab-CD3), came out in 1986. It was based on research by scientists Kohler and Milstein, who developed a method using mice to create antibodies.

But there was a problem—because the antibody was made from mouse proteins, the human body saw it as foreign and attacked it, which caused side effects and made the treatment less effective.

Luckily, later advances in genetic engineering helped overcome this issue and allowed monoclonal antibodies to become safer and more widely used in medicine.

Chimeric Monoclonal Antibodies

As scientists learned how to work with genes, they developed a new type of monoclonal antibody called chimeric antibodies. These are part mouse and part human.

However, the results were mixed—some of these chimeric antibodies worked well, while others still caused unwanted immune reactions.

Humanized Monoclonal Antibodies

Humanized antibodies took this idea even further. Instead of keeping large parts of the mouse antibody, only the tiny regions that directly bind to the target (called CDRs) were kept from the mouse. The rest was replaced with human parts.

Sometimes, changing the surrounding regions altered the shape of the antibody so much that it didn’t bind as well to its target.

The Current Landscape 

The latest types of monoclonal antibodies are called fully human antibodies, meaning they don’t contain any mouse parts. There are two main ways to make them:

Genetically Modified Mice

In this method, scientists use special mice that have human antibody genes. These mice produce antibodies that are fully human. An example is Vectibix® (approved in 2006).

Phage Display

It is a lab technique where scientists use viruses that infect bacteria (called phages) to test many different versions of antibody parts (called CDRs) to find the ones that bind best to a target.

These best-fitting parts are then added to a human antibody structure. Humira® (approved in 2002) was made this way.

Fully human antibodies tend to cause fewer immune reactions than earlier types, but they can still trigger some responses depending on the product and what it’s used for.

What Does The Future Hold?

It’s hard to say exactly what’s next, but antibody technology keeps improving. Scientists are now using computer models (“in silico”) to design antibodies that are less likely to cause immune reactions.

They’re also exploring a newer method called yeast display, which may work better than phage display.

Additionally, advanced genetically engineered mice with even more human antibody genes are helping create better treatments.

To Wrap Up

No matter how the next generation of monoclonal antibodies is made, one thing is clear: these powerful therapies can do things that regular drugs often can’t. They will continue to play a big role in treating diseases for many years to come.