Labor für Zelltherapie
Decades of work in basic and tumor immunology research have identified key factors hampering proper anti-tumor immune response, including suppressive T cells, immune checkpoints as well as suppressive cytokines secreted by tumor- and antigen presenting cells. Such discoveries have led to the development of many cancer drugs that revolutionized cancer treatment.
While tumor immunology research is currently directed towards the study of inhibitory surface markers, such as PD-1, CTLA-4, TIGIT and TIM3, we focus on the deep see where epigenetic factors shove the immune dysfunction in cancer patients. The search for transcriptional factors that initiate the first signals for T cell exhaustion, in cancer patients, lead to the identification of novel drug targets that would reinforce tumor immunotherapy.
As a part of the largest study group focusing on Multiple Myeloma in Germany, German-speaking Myeloma Multicenter Group “GMMG”, we utilize the combination of clinical outcomes gathered through our clinical trial with high throughput genomics approaches, as well as T cell functional assay, to investigate the transcriptional pathways that are involved in tumor escape mechanisms.
Our Laboratory approaches include: Flow Cytometry, RT-PCR, Western Blotting, CRISPR Cas9 Knock out, RNA bulk Seq, Single Cell Seq, Luciferase Reporter Assay, ELISA and ELISPOT.
Our current projects:
- The Immunomodulatory Impact of IKZF3 expression on T cells in patients with Multiple Myeloma.
- Immuno-reconstitution analyses of patients enrolled within the GMMG-HD7 clinical trial.
- The Identification of transcriptional factors that guide CD8+ cells towards exhaustion state in cancer patients.
Universitätsmedizin der Johannes Gutenberg-Universität Mainz (AG Echchannaoui)
Division of Applied Bioinformatics (AG Brors)
Universitätsklinikums Erlangen (AG Bruns)
- K. Kriegsmann, M.-A. Baertsch, M.H.S. Awwad, M. Merz, D. Hose, A. Seckinger, A. Jauch, N. Becker, A. Benner, M.S. Raab, J. Hillengass, U. Bertsch, J. Dürig, H.J. Salwender, M. Hänel, R. Fenk, M. Munder, K. Weisel, C. Müller-Tidow, H. Goldschmidt, M. Hundemer, Cereblon-binding proteins expression levels correlate with hyperdiploidy in newly diagnosed multiple myeloma patients, Blood Cancer J. 9 (2019)
- K. Kriegsmann, M. Kriegsmann, M. Cremer, M. Schmitt, P. Dreger, H. Goldschmidt, C. Müller-Tidow, M. Hundemer, Cell-based immunotherapy approaches for multiple myeloma, Br. J. Cancer 120 (2019)
- M.H.S. Awwad, K. Kriegsmann, J. Plaumann, M. Benn, J. Hillengass, M.S. Raab, U. Bertsch, M. Munder, K. Weisel, H.J. Salwender, M. Hänel, R. Fenk, J. Dürig, C. Müller-Tidow, H. Goldschmidt, M. Hundemer, The prognostic and predictive value of IKZF1 and IKZF3 expression in T-cells in patients with multiple myeloma, Oncoimmunology 7 (2018)
- J. Plaumann, M. Engelhardt, M.H.S. Awwad, H. Echchannaoui, E. Amman, M.S. Raab, J. Hillengass, N. Halama, B. Neuber, C. Müller-Tidow, H. Goldschmidt, M. Hundemer, IL-10 inducible CD8+ regulatory T-cells are enriched in patients with multiple myeloma and impact the generation of antigen-specific T-cells, Cancer Immunol. Immunother. 67 (2018)
- B. Neuber, J. Dai, W.A. Waraich, M.H.S. Awwad, M. Engelhardt, M. Schmitt, S. Medenhoff, M. Witzens-Harig, A.D. Ho, H. Goldschmidt, M. Hundemer, Lenalidomide overcomes the immunosuppression of regulatory CD8+CD28- T-cells, Oncotarget 8 (2017)
- A. Seckinger, J.A. Delgado, S. Moser, L. Moreno, B. Neuber, A. Grab, S. Lipp, J. Merino, F. Prosper, M. Emde, C. Delon, M. Latzko, R. Gianotti, R. Lüoend, R. Murr, R.J. Hosse, L.J. Harnisch, M. Bacac, T. Fauti, C. Klein, A. Zabaleta, J. Hillengass, E.A. Cavalcanti-Adam, A.D. Ho, M. Hundemer, J.F. San Miguel, K. Strein, P. Umaña, D. Hose, B. Paiva, M.D. Vu, Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment, Cancer Cell 31 (2017)
- I. Krämer, M. Engelhardt, S. Fichtner, B. Neuber, S. Medenhoff, U. Bertsch, J. Hillengass, M.-S. Raab, D. Hose, A.D. Ho, H. Goldschmidt, M. Hundemer, Lenalidomide enhances myeloma-specific T-cell responses in vivo and in vitro, Oncoimmunology 5 (2016)
- S. Fichtner, D. Hose, M. Engelhardt, T. Meißner, B. Neuber, F. Krasniqi, M. Raab, S. Schönland, A.D. Ho, H. Goldschmidt, M. Hundemer, Association of antigen-specific T-cell responses with antigen expression and immunoparalysis in multiple myeloma, Clin. Cancer Res. 21 (2015)
- M. Munder, M. Engelhardt, D. Knies, S. Medenhoff, G. Wabnitz, C. Luckner-Minden, N. Feldmeyer, R.-H. Voss, P. Kropf, I. Müller, R. Conradi, Y. Samstag, M. Theobald, A.D. Ho, H. Goldschmidt, M. Hundemer, Cytotoxicity of tumor antigen specific human T cells is unimpaired by arginine depletion, PLoS ONE 8 (2013)