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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
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
Dr. Jan Van den Brulle
T-CURX GmbH
T-CURX GmbH

Mr. Prof. Dr. med. Kobold, Sebastian

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.

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