Process Development for Cell & Gene Therapy
Leila Amini
The Amini group works on translating T-cell therapeutics from research grade to pre-GMP status to enable clinical translation. We have a broad experience in manufacturing regulatory T-cells, effector T-cells and gene-modeified T-cells using the CRISPR-Cas-9 technology.
Research
Regulatory T-cells are a potent tool to re-balance immunological disorders and we are working on their in-depth characterization, modification and preparation for clinical studies especially in the setting of transplantation and other inflammatory conditions. We are active both in process development, establishing platform technologies and functional testing of clinically relevant T cell products. We also make use of effector T-cells that can be used to steer specific anti-pathogenic reactions e.g. against seasonal/pandemic or chronic infectious diseases. Our BMBF funded TReAT (tacrolimus-resistant anti-viral T-cell Therapy; https://treat-project.com/de/) project has its aim in generating a novel platform for the regeneration of T-cell responses against different viral specificities in presence of immunosuppression. With TReAT T cell products we can keep the unwanted and overshooting immune response e.g. organ rejection or autoimmunity under control using an immunosuppressive drug namely tacrolimus and gain a suitable anti-viral immunity boost. The same modification can be implemented in regulatory T-cells for the use in auto- or allo-inflammation. We develop and design appropriate pre-GMP manufacturing processes to prepare for technology transfer to GMP compliant manufacturing to set the fundament for translating these therapies to the clinics. Further, we are working in cooperation projects to explore and establish suitable human pre-clinical in vitro test platforms to evaluate safety and efficacy of T-cell products in line with the 3Rs, preparing proof-of-concept data strengthening reproducibility for translation and deciphering the mode of action of the T cell products. Collaborations also allow us in-depth characterization of the T cell products e.g. with CITEseq, proteomics, spectral flow cytometry and off-target evaluation, which is especially important in regards to clinical safety of gene-edited T-cell therapeutics. Our junior group is strongly connected to the GMP facility of the Berlin Center of Advanced Therapies (BeCAT), the infectiology of the Charité-Universitätsmedizin to test our pathogen-specific T-cells in relevant human models, the Deutsches Rheuma-Forschungszentrum (DRFZ), clinical partners from the Charité and many fellow groups from the Berlin Center of Health (BIH) Center for Regenerative Therapies.
Methods
Methods
Cell culture
In-vitro toxicity assays
Advanced cell manufacturing/pre-GMP
Process development towards GMP
Flow cytometry, spectral flow cytometry
Innovative in-vitro models with cooperation partners
Team
Team
PI: Dr. Leila Amini, background in molecular medicine, head of the regulatory affairs unit at the BeCAT.
Post-Doc: Dr.
- Dr. Lisa Burkhardt, background in biology
- Dr. Shabnam Hemmati-Sadeghi, background in molecular biology
Doctoral students:
- Niklas Wiese, background in biotechnology
- Ghazaleh Zarrinrad, background in molecular biology (shared with Volk and Schmueck-Henneresse groups)
- Ugarit Daher, background in biotechnology (shared with CUSCO)
- Claudia Beltran-Mestres, background in advanced immunology (shared with Volk group)
- Abdolreza Nazari, background in biochemistry (shared with Reinke group)
Publications
Publications
Wendering DJ*, Amini L*, Schlickeiser S, Farrera-Sal M, Schulenberg S, Peter L, Mai M, Vollmer T, Du W, Stein M, Hamm F, Malard A, Castro C, Yang M, Ranka R, Rückert T, Durek P, Heinrich F, Gasparoni G, Salhab A, Walter J, Wagner DL, Mashreghi MF, Landwehr-Kenzel S, Polansky JK, Reinke P, Volk HD, Schmueck-Henneresse M. Effector memory-type regulatory T cells display phenotypic and functional instability. Sci Adv. 2024 Sep 6;10(36):eadn3470. *contributed equally DOI: 10.1126/sciadv.adn3470
Amini L., Kaeda J., Weber O., Reinke P. (2024) Low-dose Interleukin-2 Therapy: Fine-tuning Treg in Solid Organ Transplantation?. Transplantation. https://doi.org/10.1097/TP.0000000000004866
Amini L., Kaeda J., Fritsche E., Roemhild A., Kaiser D., Reinke P. (2023) Clinical adoptive regulatory T Cell therapy: State of the art, challenges, and prospective. Front Cell Dev Biol. https://doi.org/10.3389/fcell.2022.1081644
Peter, L., Wendering, D. J., Schlickeiser, S., Hoffmann, H., Noster, R., Wagner, D. L., Zarrinrad, G., Münch, S., Picht, S., Schulenberg, S., Moradian, H., Mashreghi, M. F., Klein, O., Gossen, M., Roch, T., Babel, N., Reinke, P., Volk, H. D., Amini, L.* & Schmueck-Henneresse, M.* (2022). Tacrolimus-resistant SARS-CoV-2-specific T-cell products to prevent and treat severe COVID-19 in immunosuppressed patients. Mol Ther Met Clin Dev. https://doi.org/10.1016/j.omtm.2022.02.012*contributed equally
Amini L., Silbert S.K., Maude S.L., Nastoupil L.J., Ramos C.A., Brentjens R.J., Sauter C.S., Shah N.N., Abou-El-Enein M. (2022). Preparing for CAR T cell therapy: patient selection, bridging therapies and lymphodepletion. Nat Rev Clin Oncol. https://doi.org/10.1038/s41571-022-00607-3.
Amini, L., Wagner, D. L., Rössler, U., Zarrinrad, G., Wagner, L. F., Vollmer, T., Wendering, D. J., Kornak, U., Volk, H. D., Reinke, P., & Schmueck-Henneresse, M. (2021). CRISPR-Cas9-Edited Tacrolimus-Resistant Antiviral T-cells for Advanced Adoptive Immunotherapy in Transplant Recipients. Molecular Therapy. https://doi.org/10.1016/j.ymthe.2020.09.011
Amini L., Greig J., Schmueck-Henneresse M., Volk H.-D., Bézie S., Reinke P., Guillonneau C., Wagner D.L., Anegon I. (2021). Super-Treg: Toward a New Era of Adoptive Treg Therapy Enabled by Genetic Modifications. Front Immunol. https://doi.org/10.3389/fimmu.2020.611638
Amini, L., Vollmer, T., Wendering, D. J., Jurisch, A., Landwehr-Kenzel, S., Otto, N. M., Jürchott, K., Volk, H. D., Reinke, P., & Schmueck-Henneresse, M. (2019). Comprehensive characterization of a next-generation antiviral T-cell product and feasibility for application in immunosuppressed transplant patients. Front Immunol. https://doi.org/10.3389/fimmu.2019.01148