Cancer therapy with smart ‘umbrellas’ spares healthy body tissue

Cancer remains one of the leading causes of death in the Netherlands. Fortunately, researchers are making a lot of progress when it comes to effective therapies. Bauke Albada and his colleagues are working at Wageningen University & Research (WUR) on a groundbreaking technique that better navigates antibodies, substances that attack cancer cells, to a tumor. “This way we save healthy tissue and avoid unwanted side effects.”

There is a passionate atmosphere in the WUR laboratories. Bauke Albada, associate professor of bio-organic chemistry, and his team are busy developing an innovative technique in the fight against cancer. They have received a grant from the Open Technology program of the Netherlands Organization for Scientific Research (NWO). In a collaboration between WUR, Radboud University Medical Center and a consortium of companies, natural and modified antibodies are being examined. These play a crucial role in the body’s immune response against cancer because they can bind to cancer cells or to substances secreted by cancer cells.

In the right place in the body

It is essential to get these antibodies in the body at the right time and in the right place. However, with regular cancer therapies based on antibodies, this is not always the case. With the grant, the researchers can now improve these therapies. Albada: “The main goal of the research is to prevent antibodies from ‘sticking’ to healthy tissue along the way and to better navigate to the cancer cells. This way we spare healthy tissue and avoid unwanted side effects. In addition, as we improve the efficacy of the therapy, the dose can be adjusted.”

In more detail: WUR and Radboudumc are looking at so-called stealth antibodies, in other words, antibodies that are modified and can be selectively activated in the tumor microenvironment. WUR creates the desired constructs, they are tested in Nijmegen to see whether they demonstrate the desired activity. It is a complex investigation. Yet Albada knows how to explain it visually. “You could say that we are developing a kind of ‘umbrellas’ to put on the antibodies. The antibodies move through the body like spies. Only when they arrive at the place where they need to be do they throw off their umbrella. They then eliminate the cancer cells.”

Albada and his colleagues are currently investigating different ways to get the antibodies to the right place in the body. “We can test fifty different ways in the lab. For example, we work with toxins, but also with components that activate the immune system. The body itself is put to work.” The team is also investigating which decoupling mechanisms work best. Once they arrive at the site, the antibodies must be released from their umbrella. Albada: “Can we just cut the stick, or is that not desirable? We have to find an answer to those kinds of questions.”

Unique approach

The research is innovative. Although the ‘umbrella technique’ has been researched before, there was much room for improvement. “Our predecessors opted for a biological approach. We work with synthetic biomolecules, which ensures that the process runs optimally. With our method we can create and test a new variant within a month. This way we can continue working efficiently if we encounter problems with one of our variants. And I certainly expect that those problems will come. After all, that is part of doing research.”

Putting it into practice

Ultimately, Albada wants to identify five effective candidate therapies. “We then have to incorporate them into an antibody that we have not genetically modified.” Some of the studies are being conducted at biotechnology companies Synaffix, Genmab, and EnzyTag, with which WUR researchers have previously collaborated. “It is a valuable collaboration that also allows us to implement our new findings in practice, which is also an important condition for obtaining the grant.”

Although it is still too early to say for certain, Albada is optimistic about a possible breakthrough. “I certainly foresee new possibilities. Ideally, we will arrive at a new method that is interesting for many pharmaceutical companies.” If that is the case, the research could lead to better treatment options for many patients.