Break through the tumor's protective shield

Date:
October 12, 2021
Source:
University of Vienna
Summary:
The immune system protects the body from cancer. To protect healthy
body cells from its own immune system, they have developed a
protective shield: the protein CD47 is a so called 'don't eat me'
signal, which tells the immune cells to stand back. Tumor cells
exploit this CD47-based protection strategy for evading the immune
system, by increasing presentation of CD47 on their cell surface. A
team has now developed a therapy concept for programming the tumor
cells to produce on their own a CD47-blocking and immune-activation
fusion protein. This therapy approach could stop tumor growth.



FULL STORY ==========================================================================
On phagocytic cells, also called macrophages, and other immune cells the
ligand for CD47, namely SIRPa, can be found. When SIRP? binds to CD47,
this triggers a signal which prevents the killing of the target cell. Most tumor cells also produce high amounts of CD47 and hence prevent being
attacked by immune cells.

Current tumor 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 tumor cells on
their own produce a CD47-blocking and immune activating protein. For
this, scientists introduced a DNA gene vector into the tumor cells. DNA sequences were designed to ensure the expression of a protein with
maximized CD47-blocking and immune activating properties. After successful
DNA transfer, tumor cells produced and secreted the protein into the
tumor vicinity.

Results: CD47 was successfully blocked not only on tumors cells
producing the fusion protein but also on the tumor cells in
their vicinity. Tumor growth was stopped and one third of tumors
were eradicated, when applying this therapy in an in vivo model
of highly malignant human breast cancer. "We observed a tumor
infiltration of macrophages, which was due to the therapy. Also,
other immune cells recognized and destroyed tumors 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 optimization of this approach, which should enable further preclinical studies paving the way for a potential new tumor therapy." ========================================================================== Story Source: Materials provided by University_of_Vienna. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Magdalena Billerhart, Monika Scho"nhofer, Hemma Schueffl, Wolfram
Polzer,
Julia Pichler, Simon Decker, Alexander Taschauer, Julia Maier,
Martina Anton, Sebastian Eckmann, Manuel Blaschek, Petra Heffeter,
Haider Sami, Manfred Ogris. CD47-targeted cancer immunogene therapy:
secreted SIRPa-Fc fusion protein eradicates tumors by macrophage
and NK cell activation.

Molecular Therapy - Oncolytics, 2021; DOI:
10.1016/j.omto.2021.09.005 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211012095026.htm

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