First steps toward new cancer vaccine

22 May 2018

In order to reduce cancer mortality, there is a great need for new treatments. In the last few years, there have been many studies into immunotherapy.

Tim Hutten, theme Cancer development and immune defense has been studying the interactions between immune cells and cancer cells. He carried out research into two receptors that could be the first step toward creating a cancer vaccine. Such a vaccine could stimulate the body’s immune cells to destroy cancer cells. Hutten conducted his research on culture cells in a laboratory. Further research will reveal whether the vaccine can be manufactured and whether it is safe. Hutten defended his PhD thesis on 18 May 2018.

In the past five years, the application of immunotherapy has gone through a developmental acceleration. Hutten studied the role of dendritic cells against different forms of cancer. Dendritic cells are part of our immune system. In dendritic cell vaccination, dendritic cells are injected into the patient’s body. These cells recognize foreign bodies, such as tumors. They remove protein-based parts of the tumor cell and present these on their surface. Other immune cells recognize this signal, causing them to destroy the tumor cell.

A new receptor

Hutten used a receptor (CLEC12A) on the dendritic cells to activate the immune cells. Hutten: “I bound pieces of cancer cells to antibodies. These antibodies fit perfectly on the CLEC12A receptor. This works like a key in a lock. When the CLEC12A receptors bound to the antibodies with the pieces of cancer cells, the dendritic cells activated many more immune cells.” This receptor is a great starting point for further research into a vaccine. If such a vaccine would contain parts that can bind specifically to this receptor, the body would activate more immune cells against the tumor.

Activating and inhibiting substances

Tumor cells produce various proteins, which they deposit in their environment. Some proteins stimulate immune cells into destroying the tumor, while others, conversely, inhibit the immune cells. The sum of activating and inhibiting proteins determines how strong the immune reaction will be. Hutten also carried out research with a receptor (PD-L1) on the tumor cells that binds to an immune cell. This binding causes the immune cell to stop its attack against the tumor cell. Hutten: “This binding is something we want to impede. We have therefore inhibited the expression of the PD-L1 receptor on the cancer cell using a short piece of RNA. This caused the immune cells to remain active.”

The PD-L1 receptor also forms a starting point for further research into a vaccine. If the vaccine would contain short pieces of RNA of PD-L1, the cancer cells would form fewer bonds with the immune cells, in turn causing the immune reaction against the cancer cells to be stronger. Hutten performed his entire research on culture cells in a laboratory. It can therefore not yet be said whether these methods will work in humans nor whether they are safe. Further experiments will answer these questions.

Vaccine

Researchers at Radboudumc are currently working on a vaccine that works on both receptors Hutten used in his research. This vaccine can both activate dendritic cells and remove the immune reaction-inhibiting environment of the tumor.