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How to steal the protective shield of a tumor

13.10.2021

At the Department of Pharmaceutical Sciences, a research team has developed a therapeutic approach that could stop tumors from growing.

The immune system protects the body against the development of cancer. To prevent immune cells from turning against healthy cells, they form their own protective shield: the protein CD47 is a "don't eat me" signal, telling immune cells not to attack them. But tumor cells also take advantage of this signal by presenting increased amounts of CD47 on their cell surface. At the Department of Pharmaceutical Sciences from the Faculty of Lifesciences, a research team led by Manfred Ogris has now developed a therapeutic approach with which the tumor cells themselves produce a CD47-blocking and thus immune-activating fusion protein. This therapy can stop tumor growth.

A ligand for CD47, the protein SIRPα, is found on macrophages and other immune cells. When SIRPα binds to CD47, this interaction prevents destruction of the target cell. Most tumor cells produce increased amounts of CD47 and thus build up a protective shield against immune cells. Previous therapies with antibodies block the CD47 protein and thus activate immune cells at the same time. However, this can have considerable side effects, as it also damages healthy tissue and red blood cells.  

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Publication in Molecular Therapy Oncolytics:

CD47-targeted cancer immunogene therapy: secreted SIRPα-Fc fusion protein eradicates tumors by macrophage and NK cell activation: Manfred Ogris et al.

https://doi.org/10.1016/j.omto.2021.09.005

 

 

Macrophages (gray) attack tumor cells (green) (© Manfred Ogris & Magdalena Billerhart)