Page 29 - SaxoCell Annual Report22/23

CAR- CAR-NK4.0
NK

The project is developing an AI-assisted CAR-NK cell platform (CAR-NK4.0) and a fully automated
manufacturing process for the phase I trial of an allogeneic target-specific CAR-NK approach for
the treatment of myeloid neoplasms, using innovative technologies such as biospecific targeting,
AAV and lentiviral gene transfer, and novel cell activation.

Project Lead: Ulrike Köhl

Partners: Fraunhofer IZI, Leipzig University Hospital, Leipzig University, Chemnitz Hospital,
Affimed GmbH, Miltenyi Biotec B.V. & Co. KG

In a proof-of-concept study, a digitally controlled, automated production of CAR-NK cells with
targeted CARs was established. Here, primary Natural Killer Cells were isolated from leukocyte
concentrates to supply project partners with NK cells. The Natural Killer Cell Transduction (NKCT)
process was transferred and quality control was implemented. In addition, a first production run of
targeted CAR-NK cells with preclinical vector is planned.

A protocol was established for the clinical trial "Bridging to Transplantation" in myeloid diseases.
Patients with unfavorable prognosis and without transplantation option will receive target-specific
CAR-NK cells here. The study includes design, endpoints, patient selection and monitoring.
Biobanking will support the research during the study. The implementation of CAR-T cell therapy
has also created a suitable infrastructure for ATMP testing. In addition, the cell therapy expertise
of all project partners strengthens the planned study quality.

In the field of multiple myeloma, bi-specific CARs could be developed. Antibody fragments were
cloned into CARs suitable for NK cells and tested on target cells. Optimized CAR-NK cell
production using retroviral transduction and bispecific targeting against CD19 was successfully
tested on tumor cell lines.

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