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                  Project 5

                  Augmentation of anti-tumor efficacy of integrin αvβ3-specific CAR T cells

                  Academic Partners
                  Prof. Dr. med. Michael Hudecek
                  Medizinische Klinik II, UKW
                  publications
                  more on the person
                  PD Dr. rer. nat. Thomas Nerreter
                  Medizinische Klinik II, UKW
                  Dr. Miriam Alb
                  Medizinische Klinik II, UKW
                  Industry Partners
                  Dr. Ulf Grawunder
                  T-CURX GmbH
                  publications
                  Dr. Jan Van den Brulle
                  T-CURX GmbH
                  T-CURX GmbH
                  Collaborators

                  Prof. Dr. med. Sebastian Kobold

                  Abt. Klinische Pharmakologie, Klinikum der Universität München

                  Project Summary

                  In contrast to the very successful use of CD19-specific CAR T cells for the treatment of various leukemias and lymphomas, the therapeutic efficacy of CAR T cells against solid tumors has been very limited to date. One of the main reasons for this is the immunosuppressive tumor microenvironment. Preclinical studies have shown that equipping CAR T cells with accessory molecules such as co-receptors and chemokine receptors can significantly improve efficacy in such entities.

                  We were able to identify novel strategies that lead to a significant increase in CAR T cell function, including the modulation of transcription factors and the use of a cytokine superagonist. The aim of this project is to combine these novel strategies with chemokine receptors and to define the optimal T cell subsets for modification and thus significantly improve the therapeutic options.

                  Project related publications

                  Ataide, M. A., Komander, K., Knopper, K., Peters, A. E., Wu, H., Eickhoff, S., Gogishvili, T., Weber, J., Grafen, A., Kallies, A., Garbi, N., Einsele, H., Hudecek, M., Gasteiger, G., Holzel, M., Vaeth, M., & Kastenmuller, W. (2020). BATF3 programs CD8(+) T cell memory. Nat Immunol, 21(11), 1397-1407. doi:10.1038/s41590-020-0786-2

                  Monjezi, R., Miskey, C., Gogishvili, T., Schleef, M., Schmeer, M., Einsele, H., Ivics, Z., & Hudecek, M. (2017). Enhanced CAR T-cell engineering using non-viral Sleeping Beauty transposition from minicircle vectors. Leukemia, 31(1), 186-194. doi:10.1038/leu.2016.180

                  Sommermeyer, D., Hudecek, M., Kosasih, P. L., Gogishvili, T., Maloney, D. G., Turtle, C. J., & Riddell, S. R. (2016). Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia, 30(2), 492-500. doi:10.1038/leu.2015.247

                  Wallstabe, L., Mades, A., Frenz, S., Einsele, H., Rader, C., & Hudecek, M. (2018). CAR T cells targeting alpha(v)beta(3) integrin are effective against advanced cancer in preclinical models. Adv Cell Gene Ther, 1(2). doi:10.1002/acg2.11


                  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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                  • About BAYCELLator
                  • Projects
                    • Project 1
                    • Project 2
                    • Project 3
                    • Project 4
                    • Project 5
                    • Project 6
                    • Project 7
                    • Project 8
                  • Publications