Page 47 - SaxoCell Annual Report22/23

Mod. TheraSTAR
ATMP

TheraSTAR develops theranostic target molecules, i.e. target molecules that are important for
therapy and diagnostics, which can be used in a variety of ways for tumor immunotherapy based
on adapter RevCAR technologies, modulation of the tumor microenvironment, tumor and therapy
monitoring by diagnostic imaging methods, and radionuclide therapy.

Project lead: Anja Feldmann

Partners: TUD Dresden University of Technology, Helmholtz-Zentrum Dresden-Rossendorf

For effective and safe tumor detection and therapy, we are developing "gated positive" (GP) and
"gated inhibitory" (GI) adapter CAR (RevCAR) platforms consisting of two main components: the
target molecules (TMs) and the GP/GI-CAR T cells. The unique feature is that GP/GI-CAR T cells can
recognize and kill tumor cells exclusively mediated by the soluble TMs. The TMs determine the
tumor specificity of the GP/GI-CAR-T cells and allow their activity to be turned on and off as
needed.

The development of the platforms involves the generation of novel, bispecific target molecules
(bsTMs) that specifically target the adapter CAR-T cells against tumor-associated antigens or
"immune checkpoint" molecules. This is done to modulate the tumor microenvironment to favor
immunotherapies.

To date, novel TMs have been successfully constructed, eukaryotically expressed and purified by
affinity chromatography. In addition, GP/GI-CAR-T cells were successfully generated by lentiviral
transduction at cell culture scale. Both components were manually prepared in sufficient quantity
and quality for preclinical studies. For preclinical feasibility studies, we used tumor cell lines
presenting the target antigen natively on their surface as well as established reproducible cell
culture models recombinantly expressing the target antigen after genetic modification by lentiviral
transduction.

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