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”.