Experimental & Translational hematology
@ Jürgen Kuball 
Main focus of my research group is to redirect the immune system against cancer (stem) cells while preserving normal tissue. This work includes translational basic research as well as the implementation of phase I clinical (gene therapy) trials.
Multiple strategies are investigated: In work package 1 (
see downloads) we investigate whether T cells can be re-directed by broadly tumor-reactive second-generation T-cell receptors against cancer cells. In work package 1, work package 2 and work package 3 my group is in particular interested in
gd T cells and their unique ability to mediate anti-cancer reactivity while normal tissue is preserved and we ask whether such immuno-therapies can target the cancer stem cell. Therefore, we investigate which ligands are recognized by
gd T cells and analyze the biological role of
gd T cells in stem cell transplantation. Furthermore, we analyze leukemic cells and leukemic stem cells for expression of ligands recognized by
gd T cell receptors. Work package 4 analyses T cell immune responses in cancer patients after vaccination with tumor antigens and work package 5 analyzes the role of B cells in stem cell transplantation as host B cells seem to be involved in both, acute and chronic graft versus host disease. Understanding biology of B cells in allogeneic stem cell transplantation will therefore also improve current efforts to redirect the immune system against cancer cells.
Department of Hematology
Members
- Liane de Boome (Haematologist)
- Suzanne van Dorp (PhD student)
- Cordula Gründer (PhD student)
- Samantha Hol (technician)
- Sabine Heijhuurs (technician)
- Kirsten Scholten (Post Doc)
- Zsolt Sebestyen (Post Doc)
- Cristina Mansilla Puerta (Post Doc)
- Wouter Scheper (PhD Student)
- Julia Scherpner (Data-manager)
Kuball J, Hauptrock B, Malina V et al.
Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain.
J.Exp.Med. 2009;206:463-475 (IF 15,6)
Kuball J, Dossett ML, Wolfl M, Ho WY, Voss RH, Fowler C et al.
Facilitating matched pairing and expression of TCR chains introduced into human T cells.
Blood 2007;109(6):2331-8 (IF 10,4)
Wolfl M, Kuball J, Ho WY, Nguyen H, Manley TJ, Bleakley M et al.
Activation-induced expression of CD137 permits detection, isolation and expansion of the full repertoire of CD8+ T-cells responding to antigen without requiring knowledge of epitope-specificities.
Blood 2007; 110(1):201-10 (IF 10,4)
Su Z., Kuball J., Barreiros A.P., Gottfried D., Antunes Ferreira E., Theobald M., Galle P.R., Strand D., Strand S.
Nitric oxide promotes resistance to tumor suppression by cytotoxic T lymphocytes.
J Immunol, 2006;176(7):3923-30 (IF 6,3)
Kuball J, Schmitz F.W., Voss R.H., Ferreira E.A., Engel R., Guillaume P., Strand S., Romero P., Huber C., Sherman,L.A., Theobald,M. Cooperation of Human Tumor-Reactive CD4(+) and CD8(+) T Cells after Redirection of Their Specificity by a High-Affinity p53A2.1-Specific TCR.
Immunity. 2005;22:117-129. (IF 18,6)
Kuball J., Theobald M., Antunes Ferreira E., Hess G., Burg J., Maccagno G., Barreiros A.P., Lüth S., Schimanski C.C., Schuchmann M., Schwarting A., Otto G., Galle P.R., Lohse A.W.
Control Of Organ Transplant-Associated Graft-Versus-Host Disease (GvHD) By Host Lymphocyte Infusions (HLI).
Transplantation, 2004, 78(12): 1774-1779. (IF 4,0)
Stanislawski T., Voss R.H., Lotz C., Sadovnikova E., Willemsen R.A., Kuball J., Ruppert T., Bolhuis R.L., Melief C.J., Huber C., Stauss H.J., Theobald M.
Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer.
Nat Immunol 2001, 2:962-970. (IF 27,6)
2011-2016
Linking innate and adaptive immunity (ZonMW, VIDI)
2008-2014
Redirecting T-cells by broadly tumor-reactive second-generation T-cell receptors (ZonMW, Translational Gene Therapy Grant ZonMW)
2010-2014
Analyzing γδT-cells after allogeneic stem cell transplantation: Guiding to a new concept of T-cell based immunotherapies?. (LSBR)
2010-2014
Analyzing leukemia-reactive TCRs (KWF)
2010-2013
Molecular characterization of cancer reactive TCRs (AICR)