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Project 3

Intelligent Process Automation (IPA)

Academic Partner
Prof. Dr. med. Dirk H. Busch
Institut für Medizinische Mikrobiologie und Hygiene - TUM. Deputy Spokesman BAYCELLator
publications
more on the person
Industry Partner
Juno Therapeutics GmbH, a Bristol Myers Squibb Company (BMS)
Bristol Myers Squibb
Collaborators

Prof. Dr. rer. nat. Gabriele Multhoff

Zentralinstitut für Translationale Krebsforschung der Technischen Universität München

Prof. Dr. med. Sebastian Kobold

Abteilung für Klinische Pharmakologie, KUM

Prof. Dr. med. Dr. rer. nat. Michael von Bergwelt-Baildon

Medizinische Klinik III, KUM

Prof. Dr. med. Tobias Feuchtinger 

Universitätsklinikum Freiburg

Prof. Dr. med. Michael Hudecek 

Medizinische Klinik II, UKW

Project Summary

This joint project between BMS and MIH is aiming at the preclinical and prospective clinical evaluation of the Intelligent Process Automation (IPA) platform, an automated, ultra-short, and closed-loop CAR T cell manufacturing platform.

The proposed project focuses on an in-depth preclinical investigation of functional, immunological, and cellular properties of IPA-generated T cell products in vitro as well as in humanized in vivo mouse models. The potential to generate a more homogeneous and effective T cell product using cutting-edge manufacturing methodologies (e. g. CRISPR-mediated targeted integration) in the automated IPA production system will be evaluated by comparison with conventionally produced cells.

The preclinical data will serve as the basis for initiating technology transfer activities to a pilot production facility to establish and validate the IPA process in a GMP-compliant manufacturing environment, followed by clinical evaluation, if applicable.

Project related publications

Cossarizza, A., Chang, H. D., Radbruch, A., Acs, A., Adam, D., Adam-Klages, S., . . . Zychlinsky, A. (2019). Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). Eur J Immunol, 49(10), 1457-1973. doi:10.1002/eji.201970107

Kaeuferle, T., Stief, T. A., Canzar, S., Kutlu, N. N., Willier, S., Stenger, D., . . . Feuchtinger, T. (2022). Genome-wide off-target analyses of CRISPR/Cas9-mediated T-cell receptor engineering in primary human T cells. Clin Transl Immunology, 11(1), e1372. doi:10.1002/cti2.1372

Poltorak, M. P., Graef, P., Tschulik, C., Wagner, M., Cletiu, V., Dreher, S., . . . Germeroth, L. (2020). Expamers: a new technology to control T cell activation. Sci Rep, 10(1), 17832. doi:10.1038/s41598-020-74595-8

Radisch, S., Poltorak, M. P., Wagner, M., Cletiu, V., Radisch, C., Treise, I., . . . Germeroth, L. (2022). Next generation automated traceless cell chromatography platform for GMP-compliant cell isolation and activation. Sci Rep, 12(1), 6572. doi:10.1038/s41598-022-10320-x

Schober, K., Muller, T. R., Gokmen, F., Grassmann, S., Effenberger, M., Poltorak, M., . . . Busch, D. H. (2019). Orthotopic replacement of T-cell receptor alpha- and beta-chains with preservation of near-physiological T-cell function. Nat Biomed Eng, 3(12), 974-984. doi:10.1038/s41551-019-0409-0

Stenger, D., Stief, T. A., Kaeuferle, T., Willier, S., Rataj, F., Schober, K., . . . Feuchtinger, T. (2020). Endogenous TCR promotes in vivo persistence of CD19-CAR-T cells compared to a CRISPR/Cas9-mediated TCR knockout CAR. Blood, 136(12), 1407-1418. doi:10.1182/blood.2020005185

Contact Details

Klinikum der Universität München. Abteilung Klinische Pharmakologie 

Lindwurmstrasse 2a
80337 München
+49 089 4400 57322 Klinische Pharmakologie, KUM

Supported by the Bavarian Research Foundation - Bayerische Forschungsstiftung

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