Children's Cancer Research Center (CCRC)

Our research is composed of two pillars

1. prevention of childhood cancer focusing in acute leukemia and
2. translational cellular immunotherapy and oncolytic virotherapy against pediatric sarcoma

Prevention of cancer in children and young adults is a high goal. Cure rates of cancer are extremely high in children (80%) but disease and therapy related morbidity impact individuals quality of life and the health care system for decades. Thus our group aims at identifying children and young adults with a genetic risk for cancer and approaches, which allow modulation of the host immune response towards environmental challenges to prevent cancer. We focus on acute leukemia, the most prevalent cancer in childhood. For this purpose, we have collected an in-depth characterized cohort of n=150 transgeneration child-parent trios of children with cancer comprising clinical and genetic data. This cohort will be now extended at pediatric oncology TUM in collaboration with NCT Dresden. Combining integrated bioinformatic analysis and molecular functional assays both in-vitro as well as in-vivo, we aim to pinpoint novel signalling pathways predisposing to cancer. We further investigate the role of environmental challenges and early immune training in transgenic murine models. Training of the innate and adaptive immune system is carried out with the aim to pave the way for an early preventive strategy against childhood leukemia. This work is conducted in the context of an ERC and DKH excellence strategy funding.

Translational cellular immunotherapy and oncolytic virotherapy against pediatric sarcoma is the second research pillar. Especially advanced stages of sarcoma have a poor prognosis in children despite extensive therapy. We demonstrated that infusion of unspecific donor lymphocytes after allogeneic stem cell transplantation has the capacity to induce tumour control in paediatric sarcoma patients emphasizing the need to identify tumour-specific cellular approaches. In our hands, pediatric sarcoma has become susceptible to immunotherapy using peptide/HLA-A2 tumour specific allo-restricted wildtype- and retrovirally T cell receptor transduced T cells directed against several Ewing sarcoma (EwS) associated tumor antigens in vitro and in a preclinical mouse model. Adoptive T-cell transfer led to in vivo persistence without inducing GvHD and T cells homed to affected bone marrow and were associated with partial tumour regression (Heisenberg program - PD Dr Thiel). A BMBF granted phase I clinical study using oncolytic virotherapy in combination with CDK4/6 inhibition and immune-checkpoint inhibition will commence in 2023 in our clinic (in cooperation with Per Sonne Holm and Roman Nawroth - Department for Urology, Klinikum rechts der Isar).