Our research is focussed on the field of tumor immunology/biology with the following key aspects:
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:
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”.
Jonas S. Heitmann, Tatjana Bilich, Claudia Tandler, Annika Nelde, Yacine Maringer, Maddalena Marconato, Julia Reusch, Simon Jäger, Monika Denk, Marion Richter, Leonard Anton, Lisa Marie Weber, Malte Roerden, Jens Bauer, Jonas Rieth, Marcel Wacker, Sebastian Hörber, Andreas Peter, Christoph Meisner, Imma Fischer, Markus W. Löffler, Julia Karbach, Elke Jäger, Reinhild Klein, Hans-Georg Rammensee, Helmut R. Salih & Juliane S. Walz (2021). A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity. Nature 2021, doi: 10.1038/s41586-021-04232-5.
Bilich T, Roerden M, Maringer Y, Nelde A, Heitmann JS, Dubbelaar MS, Peter A, Hörber S, Bauer J, Rieth J, Wacker M, Berner F, Flatz L, Held S, Brossart P, Märklin M, Wagner P, Erne E, Klein R, Rammensee HGR, Salih HR, Walz JS (2021). Pre-existing and post-COVID-19 immune responses to SARS-CoV-2 in cancer patients. Cancer Discovery 2021, 1. doi: 10.1158/2159-8290.CD-21-0191
Bilich T, Nelde A, Heitmann JS, Maringer Y, Roerden M, Bauer J, Rieth J, Wacker M, Peter A, Horber S, Rachfalski D, Märklin M, Stevanovic S, Rammensee HG, Salih H, Walz JS (2021). Differential T cell and antibody kinetics delineate SARS-CoV-2 peptides mediating long-term immune response after COVID-19. Science Transl Med. 2021 Mar 15;eabf7517. doi: 10.1126/scitranslmed.abf7517
Nelde A, Bilich T, Heitmann JS, Maringer Y, Salih HR, Roerden M, Lübke M, Bauer J, Rieth J, Wacker M, Peter A, Hörber S, Traenkle B, Kaiser PD, Rothbauer U, Becker M, Junker D, Krause G, Strengert S, Schneiderhan-Marra N, Templin MF, Joos TO, Kowalewski DJ, Stos-Zweifel V, Fehr M, Rabsteyn A, Mirakaj V, Karbach J, Jäger E, Graf M, Gruber LC, Rachfalski D, Preuß B, Hagelstein I, Märklin M, Bakchoul T, Gouttefangeas C, Kohlbacher O, Klein R, Stevanović S, Rammensee HG, Walz JS (2020). SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T-cell recognition. Nature Immunol. 2021 Jan;22(1):74-85. doi: 10.1038/s41590-020-00808-x
Latifa Zekri , Fabian Vogt, Lukas Osburg , Stefanie Müller, Joseph Kauer, Timo Manz, Martin Pflügler, Andreas Maurer , Jonas S Heitmann, Ilona Hagelstein, Melanie Märklin, Sebastian Hörner, Tilmann Todenhöfer, Carsten Calaminus, Arnulf Stenzl, Bernd Pichler, Christian la Fougère, Marc A Schneider, Hans-Georg Rammensee, Lars Zender, Bence Sipos, Helmut R Salih, Gundram Jung. An IgG-based bispecific antibody for improved dual targeting in PSMA-positive cancer. EMBO Mol Med. 2021 Feb 5;13(2):e11902.doi: 10.15252/emmm.201911902. Epub 2020 Dec 29.
Salih HR, Jung G. The challenges of translation. EMBO Mol Med. 2019 Dec;11(12):e10874. doi: 10.15252/emmm.201910874. Epub 2019 Oct 18.
Märklin M, Hagelstein I, Koerner SP, Rothfelder K, Pfluegler MS, Schumacher A, Grosse-Hovest L, Jung G, Salih HR, Bispecific NKG2D-CD3 and NKG2D-CD16 fusion proteins for induction of NK and T cell reactivity against acute myeloid leukemia, J Immunother Cancer 2019 May 29;7(1):143
frontend.sr-only_#{element.contextual_1.children.icon}: Prof. Dr. med. Helmut Salih
Laboratory
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