A new study titled 'CD47-targeted cancer immunogene therapy: secreted SIRPα-Fc fusion protein eradicates tumours by macrophage and NK cell activation' shows how to break through the tumour's protective shield.
On phagocytic cells, also called macrophages, and other immune cells the ligand for CD47, namely SIRPa, can be found.
When SIRPα binds to CD47, this triggers a signal which prevents the killing of the target cell.
Most tumour cells also produce high amounts of CD47 and hence prevent being attacked by immune cells.
Current tumour therapies using antibodies could block CD47 and at the same time activate immune cells.
Nevertheless, serious side effects to healthy organs and blood cells limit this approach.
The novel therapy concept presented here ensures that tumour cells on their own produce a CD47-blocking and immune activating protein.
For this, scientists introduced a DNA gene vector into the tumour cells.
DNA sequences were designed to ensure the expression of a protein with maximised CD47-blocking and immune activating properties.
After successful DNA transfer, tumour cells produced and secreted the protein into the tumour vicinity.
CD47 was successfully blocked not only on tumours cells producing the fusion protein but also on the tumour cells in their vicinity. tumour growth was stopped and one third of tumours were eradicated, when applying this therapy in an in vivo model of highly malignant human breast cancer.
"We observed a tumour infiltration of macrophages, which was due to the therapy. Also, other immune cells recognised and destroyed tumours cells marked with fusion protein. We were relieved, that we did not observe any organ related toxicities", Manfred Ogris explains. "Next we aim at a further optimisation of this approach, which should enable further preclinical studies paving the way for a potential new tumour therapy."
Souce: University of Vienna
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