DKTK Professor for Translational Immunology
Professor Helmut Salih
Image: Electron-microscopic picture of the interaction of platelets with a tumor cells resulting in transfer of MHC class I. MHC class I on platelet-coated tumor cells was stained with post-embedding immunogold-labelling using 10nm gold particles (red dots). Gold particles densely accumulating on the platelet surface as well as at sites of focal intimate contacts of platelet (left) and tumor cell (right) membranes are indicated by arrows. Bar represents 500 nm.
Our research focuses on the field of tumor immunology/biology with the following key aspects:
- Molecular mechanisms influencing tumor-immune interaction and escape including their therapeutic modulation
- Development of novel immunotherapeutic strategies, in particular novel antibody formats and peptide vaccination strategies to induce antitumor immunity of NK and T cells until the stage of clinical studies
With regard to the molecular mechanisms underlying host-tumor interaction, we analyze the expression and function of various immunoregulatory molecules, in particular the NKG2D/NKG2D ligand molecule system and various members of the TNF/TNFR family, in immune and tumor cells (including putative tumor stem cells) and the influence of other healthy cells like e.g. platelets.
Besides their pathophysiological role we study the possibilities to modulate the respective molecules/cells to avoid tumor immune escape. This aims, among others, to improve the efficacy of presently available therapeutic strategies that rely on a sufficient anti-tumor immune response (e.g., allogenic stem cell transplantation). 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 key aspect of our scientific interest: the development of novel Fc-optimized monoclonal and bispecific antibodies as well as modified immunoreceptor fusion proteins and peptide vaccination strategies for induction of NK and T cell anti-tumor reactivity in cancer patients. Notably, particular effort is made to develop our therapeutic compounds (i) until the stage of clinical application with (ii) substantial contribution of academia. The feasibility of this idea is demonstrated by our recent work with Fc-optimized and bispecific FLT3 antibodies, which already have been successfully applied to leukemia patients.
Overall, the superordinate goal 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 “Translational Immunology”.
Professor Dr. Helmut Salih is located at the DKTK partner site Tübingen.
Clinical Cooperation Unit for Translational Immunology
German Cancer Consortium (DKTK)
German Cancer Research Center (DKFZ)
Foundation under Public Law
Partner site Tübingen
University Hospital / Department for Internal Medicine II
Fax: +49 (0)7071/29-4391
Extract of Scientific Publications
Kowalewski DJ, Schuster H, Backert L, Berlin C, Kahn S, Kanz L, Salih HR, Rammensee HG, Stevanovic S, Stickel JS. HLA ligandome analysis identifies the underlying specificities of spontaneous antileukemia immune responses in chronic lymphocytic leukemia (CLL).
Proc Natl Acad Sci U S A. 2015 Jan 13 (Epub ahead of print)
Schmiedel BJ, Scheible CA, Nuebling T, Kopp HG, Wirths S, Azuma M, Schneider P, Jung G, Grosse-Hovest L and Salih HR: RANKL expression, function and therapeutic targeting in multiple myeloma and chronic lymphocytic leukemia.
Cancer Res. 73:683-94 (2013)
Hofmann M, Große-Hovest L, Nübling T, Pyz E, Bamberg ML, Aulwurm A, Bühring HJ, Schwartz K, Haen SP, Schilbach K, Rammensee HG, Salih HR and Jung G: Generation, selection and preclinical characterization of an Fc-optimized FLT3-antibody for the treatment of myeloid leukaemia.
Leukemia. 26: 28-37 (2012)
Placke T, Örgel M, Schaller M, Jung G, Rammensee HG, Kopp HG and Salih HR: Platelet-derived MHC Class I confers a pseudo-normal phenotype to cancer cells that subverts the anti-tumor reactivity of natural killer immune cells. Cancer Res. 72:440-8 (2012)