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. Within ImmunoINFORM, 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.

The immunosuppressive TME poses a major obstacle to effective T cellbased immunotherapies in solid cancers, leading to T cell exhaustion and treatment failure. Our group is working with advanced immunocytokines, which are innovative fusion proteins engineered for potent and localized immune activation within the tumor and it’s TME. This targeted delivery aims to reprogram immunosuppressive macrophages (e.g., M2 polarization) into active, anti-tumorigenic cells and to rejuvenate exhausted tumor-specific T cells, restoring their cytotoxic function. By concentrating immunostimulatory signals directly at the tumor site, we aim to bypass systemic toxicities associated with traditional cytokine therapies and elicit robust, long-lasting anti-cancer immunity. Our research focuses on the rational design, rigorous preclinical evaluation, and mechanistic understanding of these novel immunocytokines, paving the way for transformative treatments across a spectrum of solid malignancies. We are committed to overcoming the challenges of the TME and unlocking the full therapeutic potential of the immune system to effectively combat solid tumors.
 

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 CART 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.