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Adresse: Otfried-Müller-Str. 10
72076 Tübingen


Sekretariat

frontend.sr-only_#{element.icon}: 07071 29-83275


frontend.sr-only_#{element.icon}: 07071 29-4391


frontend.sr-only_#{element.icon}: Sabrina.augstein@med.uni-tuebingen.de


AG Salih

Scientific focus

Our research is focussed on the field of tumor immunology/biology with the following key aspects: 

  • Molecular mechanisms influencing cancer biology, host-tumor interaction and immune escape 
  • Development of novel immunotherapeutic strategies, in particular novel antibody formats to induce antitumor immunity of NK and T cells, until the stage of clinical application

With regard to the first aspect that covers our preclinical research interests, we study, among others, the expression and function of various immunoregulatory molecules in immune and tumor cells (including putative tumor stem cells). This comprises in particular the NKG2D/NKG2D ligand molecule system and various members of the TNF/TNFR family. We also analyze the influence of other cells like e.g. platelets on tumor cell biology (e.g. metastasis) and antitumor immunity. Besides their (patho)physiological role, we study the possibilities to modulate the respective molecules/cells to avoid tumor immune escape and to bolster immune surveillance. Besides increasing our general understanding of tumor immunology, this aims to improve the efficacy of presently available therapeutic strategies that rely on a sufficient anti-tumor immune response. In addition, these analyses serve to identify potential target molecules for novel therapeutic compounds (see below). Moreover, we conduct comparative analyses to identify potential differences regarding the effects of immunoregulatory molecules in mice and humans to facilitate the development of valid model systems for testing immunotherapeutic strategies prior to the application in humans.

The above described work constitutes a central basis for the second key aspect of our scientific interest: the development of novel Fc-optimized monoclonal and bispecific antibodies as well as modified immunocytokines for induction of NK and T cell anti-tumor reactivity. Notably, particular effort is made to develop our therapeutic compounds until the stage of clinical application. The feasibility of this approach is exemplified by our recent efforts with an Fc-optimized FLT3 antibody and a bispecific PSMAxCD3 antibody, which are evaluated in clinical studies:

  • FLYSYN: Multicentric clinical study evaluating an Fc-optimized FLT3-antibody for elimination of minimal residual disease (MRD) in patients with AML; (clinicaltrials.gov, NCT02789254); recruiting
  • DKTK_PMO_1605: First in human study to evaluate the safety, tolerability and preliminary efficacy of the bispecific PSMAxCD3 antibody CC-1 in patients with castration resistant prostate carcinoma; EudraCT No.: 2019-000238-20); recruitment start expected in October 2019

Overall, the superordinate goal of our work is to enable the rapid translation of results from basic science into clinical application in early clinical studies (bench to bedside), which is central for our understanding of “truly translational immunology”. 

Contact

frontend.sr-only_#{element.contextual_1.children.icon}: Prof. Dr. med. Helmut Salih


More about the person

Laboratory

frontend.sr-only_#{element.contextual_1.children.icon}: +49 7071 29-82880
+49 7071 29-82838



Team

Recent prices/awards

  • 2019Young Investigator Award, 20th International AEK Cancer Congress to Stefanie Maurer
  • 2018Abstract Achievement Award, Annual Meeting of the American Society of Hematology, San Diego to Bastian J. Schmied
  • 2017Two poster awards, Annual meeting of the DGHO, Stuttgart to Helmut Salih and Stefanie Maurer
    Best Abstract Award, Annual meeting of the DGHO, Stuttgart to Stefanie Maurer
  • 2016Abstract Achievement Award, Annual Meeting of the American Society of Hematology, San Diego to Kathrin Rothfelder
  • 2015Teaching Award (best lecturer) to Helmut Salih

Selected publications

  • Paczulla AM, Rothfelder K, Raffel S, Konantz M, Steinbacher J, Mbarga M, Wang H, Schaefer T, Tandler C, Falcone M, Nievergall E, Dörfel D, Passweg JR, Lutz C, Schwaller J, Zeiser R, Blazar BR, Caligiuri MA, Dirnhofer S, Lundberg P, Kanz L, Quintanilla-Martinez L, Steinle A, Trumpp A, Salih HR*, Lengerke C. 2019. Absence of NKG2D ligands defines human leukaemia stem cells and mediates their immune evasion. Nature 572(7768):254-259
    * Corresponding and shared senior author
  • Nuebling T, Schumacher CE, Hofmann M, Hagelstein I, Schmiedel BJ, Maurer S, Federmann B, Rothfelder K, Roerden M, Dörfel D, Schneider P, Jung G, Salih HR. 2018. The Immune Checkpoint Modulator OX40 and Its Ligand OX40L in NK-Cell Immunosurveillance and Acute Myeloid Leukemia. Cancer Immunol Res. 6(2):209-21
  • Koerner SP, André MC, Leibold JS, Kousis PC, Kübler A, Pal M, Haen SP, Bühring HJ, Grosse-Hovest L, Jung G and Salih HR. 2017. An Fc-optimized CD133 antibody for induction of NK cell reactivity against myeloid leukemia. Leukemia 31:459-69
  • Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Specchia G, Efficace F, Sborgia M, Di Bona, E, Breccia M, Cairoli R, Rambaldi A, Melillo L, La Nasa G Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F. 2017. Improved Outcomes with Retinoic Acid and Arsenic Trioxide Compared to Retinoic Acid and Chemotherapy in Non-High Risk Acute Promyelocytic Leukemia. Final Results of the Italian-German APL0406 Trial. J Clin Oncol. 35(6):605-12
  • Wild J, Schmiedel BJ, Maurer A, Raab S, Prokop L, Stevanović S, Dörfel D, Schneider P and Salih HR. 2015. Neutralization of NK cell-derived B cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis. Leukemia 29:1676-83


Patent applications

  • Anti-Cancer Combination Treatment (EP16170328.5; WO 2017198609 A1)
  • Novel PMSA Binding Antibody And Uses Thereof EP 16151281.9) 
  • Fusion proteins comprising a binding protein and an interleukin-15 polypeptide having a reduced affinity for IL15ra and therapeutic uses thereof (EP 15 157 911.7)
  • Use of blocking reagents for reducing unspecific T cell-activation (EP 14195645.8)
  • RANKL-specific agent for treating metastatic disease (EP 14193179.0; WO 2016075221)
  • Recombinant antibody molecule and its use for target cell restricted T cell activation; (PCT/EP 2013/050603; EP 14181060.6)
  • Bispecific fusion proteins for enhancing immune responses of lymphocytes against tumor cells (EP 15163460.7)
  • Improved bispecific FLT3xCD3 antigen binding proteins (EP 18193889.5)

Zertifikate und Verbände

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