PERSPECTIVES

"Looking at the future of immuno-oncology therapy"

With the first generation of immuno-oncology therapies ready to hit the market, Oncurious and VIB are already looking at the future. Their partnership seeks to combine early-stage research on five novel assets. “Combining targets is a unique opportunity to offer improved next-generation immuno-oncology therapies.”

This past year Oncurious concluded an agreement with VIB to acquire exclusive licenses to a portfolio of five innovative immuno-oncology assets. Those unique new targets originate from seminal work at the VIB-KU Leuven labs of Gabriele Bergers and Massimiliano Mazzone and the VIB-VUB lab of Jo Van Ginderachter.

“Our labs all have a different focus,” explains Jo Van Ginderachter. He is head of the Immunology labs at VIB and VUB, where his team researches immunotherapies for several diseases. The VIB-KU Leuven lab of Gabriele Bergers focuses on the vascular niches of tumors, and Massimiliano Mazzone and his team at the Angiogenesis lab of VIB and KU Leuven research inflammation and angiogenesis of tumors. “We now combine our expertise for one shared goal: to find next-generation therapies in immuno-oncology,” Jo Van Ginderachter explains.

Combinatory approach

“In past years it has been proven that our immune system is indeed able to recognize cancer cells efficiently and perform anti-tumor activity,” says Jo Van Ginderachter. Several clinical trials of immuno-oncology therapies show excellent results and some of them are already on the market. “Those first-generation therapies, like checkpoint inhibitors that help the body recognize and attack cancer cells, have already proven successful in a subset of patients,” adds Gabriele Bergers.

But many cancer patients are still not responding to the first generation of immunotherapies. “To give an example, melanomas immunotherapy is currently first in line and works very well for some 30% of patients. But what about the other 70%? Even worse is the situation for colon and pancreas cancer where the response is close to zero,” explains Massimiliano Mazzone. “That is where we want to make a difference with our unique combinatory approach.”

Gabriele Bergers continues: “We will merge our labs’ different strategies to merge five innovative compounds into one R&D pipeline. Combinatorial treatment modalities can potentially have a much better effect and reach a majority of patients.”

The research team notes several possible combinations. “We will investigate whether our assets can be complementary and beat cancer cells in a unique way. But they also can potentially be combined with first-generation immunotherapies like checkpoint inhibitors and offer a better outcome for patients. They could even improve conventional chemotherapy, to better reach and attack the tumor.”

Tumor as a complex organ

Jo Van Ginderachter explains this novel research of the VIB-Oncurious team as focusing on the ‘non-cancer’ part of tumors: “What has been partly overlooked in the past is that a tumor is a very complex organ, not just consisting of cancer cells but also containing normal cells and blood vessels. This ‘non-cancer’ part of a tumor is critical to supporting its growth, so it too can be interesting as a therapy target.”

“Conventional therapies like chemo and radiation often delay the disease instead of killing the tumor, which provides a long-term cure,” notes Massimiliano Mazzone. “The problem is that a tumor will always find other ways to grow, so often it is just a matter of time until the cancer returns. If you can use a positive force of cells that attack the cancer cells from within, you could actually remove the disease. That is the basic idea of immunotherapy: to use the body’s own immune cells to fight cancer.”

But a tumor’s complex microenvironment influences immune cell activity. “A tumor can be compared to a normal functioning organ. It is programmed to survive so it will try to prevent immune cells from entering, for example by disguising itself,” says Jo Van Ginderachter. “Our goal is to find ways to work around that.”

Trojan horse

“In essence, we want to create an immunostimulatory environment in which immune cells are able to attack cancer cells,” continues Gabriele Bergers. Her team is working on a concept to modulate the vascular system in the tumor. “We intend to create specialized blood vessels that enhance the infiltration of immune cells into the tumor.”

“Another working part of a tumor is immunosuppression by specialized cells that downregulate the function of immune cells,” notes Jo Van Ginderachter. “Lowering that immunosuppressive activity can improve immunotherapy’s working mechanism. That is what my lab is focusing on.”

Massimiliano Mazzone adds: “My team’s contribution is very similar. We see that tumors try to repulse the immune system, creating some type of barrier. We try to modify guidance cues and the ‘traffic lights’ inside the tumor to attract immune cells instead of repulsing them. Another way to attack tumors from the inside is reeducating specific cells called macrophages. These cells normally protect the body, but they’re modified by the tumor to make it stronger. If we can reeducate them to their original function they will start to attack the cancer cells like a Trojan horse.”

Collaboration as strong added value

VIB Discovery Sciences will take the lead in these projects’ preclinical development to create a new pipeline of next-generation immuno-oncology drugs. “The VIB research institute brings our labs together, yielding intense collaboration between our teams. That is a powerful added value to achieving progress in this field,” explains Jo Van Ginderachter.

“Our holistic approach looks at the concept of fighting cancer in a broad perspective. The preclinical research in these early-stage programs can lead to potential new drugs targeting a very broad spectrum of cancers. This is why the project is so exciting”, concludes Gabriele Bergers.

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Prof. Jo Van Ginderachter

Head, Laboratory of Cellular and Molecular Immunology, VUB (Vrije Universiteit Brussel), Laboratory of Myeloid Cell Immunology, VIB Center for Inflammation Research

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Prof. Gabriele Bergers

Head, Laboratory of Tumor Microenvironment and Therapeutic Resistance, VIB-KU Leuven Center for Cancer Biology

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Prof. Massimiliano Mazzone

Head, Laboratory of Tumor Inflammation and Angiogenesis, VIB-KU Leuven Center for Cancer Biology