Technique to Produce Multi-Target Antibody Therapies

Conn Hastings
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Researchers in The Netherlands and Switzerland have devised a new technique to reliably produce antibodies that can bind to two different target molecules at the same time, which could be very useful for cancer immunotherapy.

Antibodies are Y-shaped protein structures that can recognize and bind to highly specific target molecules at the tip of each “arm” of the Y structure. They are normally produced by our white blood cells, and bind to proteins on viruses and bacteria, helping us to defeat infections in the body.

However, in recent years scientists have been able to produce specific antibodies in the lab. These manufactured antibodies are now used in immunotherapy, where they can bind to specific target proteins in the body, such as those on cancer cells, stimulating the immune system to attack a tumor.

One approach that scientists have been trying to master is to create antibodies that can bind different molecules at each of their “Y” arms. These types of antibodies are called bispecific antibodies, and are much more versatile. For example, they could bring two different cells or molecules together or bind to a cluster of different proteins.

So far, scientists have had only limited success making such versatile antibodies, which have needed specialized manufacturing processes, making scale-up impossible, or have not been stable enough to use as a therapy.

In a recent development, a team of researchers have engineered bispecific antibodies, using virtual screening software to make just a few key changes to natural human immunoglobulin G (IgG) antibodies. IgG is the most abundant antibody in the human body. The team showed that the bispecific antibodies could be easily manufactured and are as stable as regular antibodies.

“We have made, in a complete IgG molecule, only four changes to get from a normal monospecific antibody into a bispecific antibody,” said John de Kruif, a researcher involved in the study. “The great thing is that it looks so much like a normal antibody that we can produce it well and we believe we know how it will behave.”

The team have made bispecific antibodies targeting cancer cell protein clusters, and these are currently in clinical trials. They are confident they can make a huge array of bispecific antibodies for future studies. “Antibodies are capable of being so specific, and you can tweak and tune them,” said Linda Kaldenberg-Hendriks, another researcher involved in the study. “With bispecific antibodies, we believe we can choose the affinities of both arms and balance them so that you can more specifically target tumors, and also recruit other cells or molecules to attack the tumor cells without many side effects. We really think it’s the way forward.”

Technique to Produce Multi-Target Antibody Therapies