Page 27 - SaxoCell Annual Report22/23

CAR- UltraCAR-T
T

The goal of the UltraCAR-T project is the development, clinical testing and economization of
innovative CAR-T cell products for the treatment of oncological diseases. The focus is on the
optimization of development and manufacturing processes with regard to production time &
production costs, as well as product quality & product functionality.

Project management: Michael Hudecek

Partners: Fraunhofer IZI, T-CURX GmbH

Prior to the start of the project, the project partner T-CURX had already evaluated a number of
different target antigens for the execution of the project. Among other things, comprehensive
going-to-clinic and going-to-market analyses were performed and it was decided to use a target
antigen in acute myeloid leukemia (AML) as the lead target antigen for the UltraCAR-T project. The
antigen shows an advantageous expression pattern, as it is highly expressed on malignant cells in
AML and Chronic Lymphocytic Leukemia (CLL) CLL on the one hand, and is undetectable or barely
detectable in healthy tissue on the other hand. In previous experiments, T-CURX had already
produced and tested different CAR constructs. The different CARs were expressed in T cells and
their efficacy against antigen+ AML cell lines was tested. In the course of the UltraCAR-T project,
confirmatory experiments were performed with the most promising CAR construct. The data
confirm previous work and demonstrate the efficacy of CAR-T cells against AML cell lines and
primary AML blasts.
Furthermore, the manufacturing time of the CAR-T cells should be significantly reduced. This was
initially tested using a semi-open, non-automated GMP manufacturing process. For this purpose,
alternative clinical manufacturing protocols were compared, which differ, among other things, in
the type of T cell activation and in the process length. The protocols were compared in terms of
cell yield, CAR expression level, functionality and gene expression. An SOP for a 7-day
manufacturing process was then developed and tested (see Figure).
Furthermore, the manufacturing time of the CAR-T cells should be significantly reduced. This was
initially tested using a semi-open, non-automated GMP manufacturing process. For this purpose,
alternative clinical manufacturing protocols were compared, which differ, among other things, in
the type of T cell activation and in the process length.
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