Bridge to Translation - Immunotherapy from Bench to Bed side
Cellular immunotherapy requires the set-up of GMP-compatible procedures. The transfer of experimental methods to clinical scale cell engineering includes
- Automation and up-scale of cell product manufacturing
- Set-up and validation of quality control
- Product characterization
- Pre-clinical data finalization for Clinical Trial Submission
For clinical scale cell engineering in a functionally closed system we chose the "CliniMACS Prodigy" device. It offers a platform for GMP-grade cell processing applications enabling fully automated washing, fractionation, cultivation, transduction and magnetic seperation of cells in a functionally closed system.
The platform´s flexibility allows production of a wide range of cell products under S2 conditions. Further, automation within this device allows harmonization of cell-production processes in case of multicentric production strategies in clinical studies.
With the electroporator "GTx" (MaxCyte) we also have a GMP-compatible platform for the production of CRISPR/Cas-engineered cell therapy products, which can be combined with our existing platform via a tube system. The new range of non-viral "genetic engineering" processes enables the development of a wide variety of innovative T-cell therapy approaches.
Set-up of the GMP-conform manufacturing process includes generation of SOP, selection of GMP-compatible reagents and up-scale of lab protocols. Pre-validation runs are performed in order to establish the manufacturing process, train staff and prepare production approval.
"MACSQuant Analyzer" offers a GCP-compatible high-throughput platform for flow-cytometry-based quality control. With a range of automated features, this flow cytometer lays the foundation for standardization of analysis and gating procedures.
- Absolute quantification of cell populations allows dosing of cell products
- Automation allows harmonization and standardization of quality control analyses in case of multicentric production
- Development of MACSQuant "Express Modes" offers fast and easy quality control analyses
Quality control strategies are set-up and validated in accordance to the requirements of regulatory authorities.
According to regulatory requirements cell products are pre-clinically characterized using established validation processes and infrastructures:
Standardly, stability assays are perfomed in order to determine the shelf-life of the cell products.
- 2 Patent Applications
- Kaeuferle T et al. Genome-wide off-target analyses of CRISPR/Cas9-mediated T-cell receptor engineering in primary human T cells. Clin. Transl. Immunol. 2022 Jan 11:e1372. doi: 10.1002/cti2.1372
- Stief TA, Kaeuferle T, Müller TR et al. Protective T-cell receptor identification for orthotopic reprogramming of immunity in refractory virus infections. Mol Ther. 2021 May 28:S1525-0016(21)00303-8. doi: 10.1016/j.ymthe.2021.05.021
- Kaeuferle T et al. CRISPR-Cas9-Mediated Glucocortioid Resistance in Virus-Specific T cells for Adoptive T Cell Therapy Posttransplantation. Mol Ther. 2020 Jun 11:S1525-0016(20)30292-6. doi: 10.1016/j.ymthe.2020.06.002.
- Kaeuferle T et al. Strategies of adoptive T-cell transfer to treat refractory viral infections post allogeneic stem cell transplantation. J Hematol Oncol. 2019 Feb 6:12(1):13. doi: 10.1186/s13045-019-0701-1