Page 41 - SaxoCell Annual Report22/23

Reg. xMac
Med.

The xMac project focuses on the development of a GMP-compliant manufacturing process for self-
renewing human macrophages from induced pluripotent stem cells for clinical investigational
drugs against solid tumors, infectious diseases and lung diseases. The focus is on broadly
applicable macrophage preparations for allogeneic transplantation.

Project lead: Michael H. Sieweke

Partner: TUD Dresden University of Technology

The xMac project develops self-renewing human macrophages for allogeneic transplantation.
Activation of self-renewal in human macrophages removes a major obstacle to their therapeutic
application, since macrophages, in contrast to T cells, could not be propagated ex vivo until now.
With our protocol, we succeeded in increasing the yield of these cells by at least a factor of 50.

Macrophages are also a very plastic cell type and can adopt a pro-inflammatory, an anti-tumor
state, or, especially in tumors, a tumor-promoting polarization state. We have removed specific
transcription factors in self-renewing macrophages that play an important role in this process.
These self-renewing, genetically modified macrophages are resistant to tumor-induced, pro-
tumorigenic M2-like polarization and will be particularly useful for cancer therapy.

Bioinformatic and functional analyses of these modified self-renewing macrophages show that
they retain M1 polarization and are resistant to tumor-induced M2 polarization. Our data suggest
that these cells will have potent antitumor activity and formed the basis for a new patent
application.

In addition, we made progress in developing a macrophage production process in xeno-free
medium up to harvesting on day 15 after induction of the embryoid body (an intermediate in our
macrophage production).

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