Pediatric oncology

Research projects

Next-generation CAR T cells for pediatric solid tumors

Bernasconi Furtwängler group  Prof. Dr. Michele Bernasconi

We aim to improve existing therapies for pediatric solid tumors and to develop more effective and less toxic treatment strategies, with a particular focus on rhabdomyosarcoma and Wilms tumor. 

Pediatric sarcomas account for approximately 15% of childhood cancers, and relapse rates remain high with an extremely poor prognosis. Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children. Two major prognostic subgroups are recognized: fusion-negative (FN) RMS, present in about 55% of patients and associated with a five-year event-free survival of ~70%, and fusion-positive (FP) RMS, present in ~20% of patients with a markedly lower five-year event-free survival of ~23%. Wilms tumor (WT), or nephroblastoma, is the most frequent renal tumor in childhood. While curative therapy is achievable in the majority of cases, patients with high-risk tumors (blastemal or anaplastic histology) have significantly poorer survival. Moreover, current treatment regimens are associated with relevant long-term sequelae, including secondary neoplasms, cardiac insufficiency, infertility, and renal impairment. 

CAR T cells are genetically engineered T lymphocytes expressing chimeric antigen receptors (CARs). CAR T-cell therapy represents one of the most promising approaches for relapsed or otherwise refractory cancers. 

Since 2018, our laboratory has focused on advancing this personalized immunotherapy by strengthening the patient’s immune capacity to recognize and attack tumors. Using proteomics, we investigate the surfaceome to identify novel targets for CAR T-cell therapy. We then perform in vitro and in vivo studies to enhance CAR T-cell activity and therapeutic efficacy.