Klinik für Kinder- und Jugendmedizin

Our work is committed to pioneering and translating next-generation cellular therapeutics to cure childhood cancer. Our research is dedicated to advancing immune cell and tumor profiling, optimizing immune modulation strategies, and developing CAR/TCR-T cell therapies to advance efficacy against solid tumors. To address the limitations of cell therapies in solid tumors, we must gain a deeper understanding of the tumor microenvironment (TME), its cellular composition, and immune evasive mechanisms. We leverage cutting-edge single-cell spatial omics through ultra-high content imaging to decode individual immune-evasive signatures in primary patient samples and samples from mouse models. 

This approach enhances our ability to predict therapy responses and guides the development of combinatorial therapies and immune cell engineering strategies. In parallel, we are working on reprogramming the TME to unlock its full anti-tumoral potential, fostering a microenvironment that enhances and sustains T cell responses. Finally, we are spearheading the development of next-generation CAR-T and TCR-T cell therapies tailored for solid tumors, with the goal of improving efficacy and overcoming barriers to durable therapeutic responses.

Comprehensive Immuno- and tumorphenotyping

Our immunophenotyping pipeline using MACSima imaging cyclic staining (MICS) enables high-resolution single-cell profiling of immune and tumor cells to uncover cellular heterogeneity, evasion signatures, functional states, and cell-cell interactions. We aim to decipher key mechanisms driving or dampening immune responses under immunotherapy in the clinical and preclinical setting by applying ultra-high content imaging and sophisticated data analysis. Additionally, we focus on the discovery of novel biomarkers and therapeutic targets, ultimately advancing precision medicine. We plan to support patient stratification by identifying therapy targets and stratifying immune statuses. Our comprehensive spatial approach focuses on improving therapy decisions and therapy evaluation in both clinical and preclinical settings, bridges translational science with clinical application, and, thereby, accelerates the development of targeted and effective immunotherapies.

CAR-/TCR-T cell therapy

While CAR- T cells are used in the clinic for treating hematologic cancers, the efficacy of CAR-T cell therapy in pediatric solid tumor setting is limited. To address limitations of conventional CAR-T technology, we have developed the adapter CAR-T cell (AdCAR-T) system. By splitting antigen recognition and CAR-T activation, introducing adapter molecules, the system allows precise quantitative as well as qualitative regulation of CAR-T activity, improving safety and efficacy (antigen evasion).
Pediatric cancers, specifically sarcomas, are characterized by low somatic mutation rates and recurrent genomic alterations, such as oncogenic fusion genes. These genetic events represent ideal therapeutic targets, but they remain difficult to address with conventional drugs. Our research focuses on leveraging engineered T cells to target these oncogenic alterations. T cells can recognize neoantigens derived from point mutations or gene fusions when presented by HLA molecules, allowing them to target previously "undruggable" cancer drivers. We aim to identify fusion gene-specific TCRs from single-cell TCR/RNA sequencing of patient samples, vaccinated individuals, and ex vivo peptide-primed T cells. Through T cell engineering, we seek to develop targeted immunotherapies for pediatric cancers, providing new treatment strategies for these challenging diseases.