(2) Sarcoma
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).
Funding
Uwe Thiel: Heisenberg-Programm – Deutsche Forschungsgemeinschaft (DFG)
- Sebastian Schober / Uwe Thiel: Bundesministerium für Bildung und Forschung (BMBF)