Prof. Dr. med. Annette Künkele-Langer
Charité - Universitätsmedizin Berlin
Campus Virchow Klinikum
Department of Pediatrics, Division of Oncology and Hematology
Augustenburger Platz 1
Tel: +49 30 450 566 132
More than half of high-risk patients with neuroblastoma, a common childhood tumor, currently die of disease.
To better attack this cancer in children, we are developing new immunotherapies using T cells, a type of white blood cell, removed from patient blood and modified in the lab.
T cells can destroy virus-infected cells and tumor cells. By changing proteins on their cell surface, it is possible to "teach" them to find neuroblastoma cells in the body and to arm them with so-called chimeric antigen receptors (CARs) to kill the tumor cells. The armed CAR-T cells are reintroduced into the patient as a new weapon to fight the cancer.
CAR-T cell therapy has worked extremely well against leukemia, but not yet against solid tumors, as these can better protect themselves from the immunotherapy attack. Our research seeks to identify and reduce these defense mechanisms, which are currently preventing cure. Together with national and international cooperation partners, we will investigate the influence of tumor cells, their environment and surrounding blood vessels on CAR-T cells to find out how these factors allow tumor cells to escape immunotherapy, then use this new knowledge to find efficient ways to shut off the devastating tumor defense mechanisms.
- Vitanza, N.A., ..., Künkele, A. et al.(2021) "Locoregional infusion of HER2-specific CAR T cells in children and young adults with recurrent or refractory CNS tumors: an interim analysis." Nature Medicine 2021; 27(9):1544-1552.
- Zirngibl, F., ..., Künkele, A. (2021) "GD2-directed bispecific trifundctional antibody outperforms dinutuximab beta in a murine model for aggressive metastasized neuroblastoma." J Immunother Cancer 2021; 9(7):e002923.
- Grunewald, L., ..., Künkele, A. (2021) "A reproducible bioprinted 3D tumor model serves as a preselection tool for CAR T cell therapy optimization." Front Immunol 2021; 12:689697.
- Koche, R.P., ..., Künkele, A. et al.(2020) "Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma." Nat Genet 2020, 52: 29-34.
- Künkele, A. et al. (2017) "Preclinical assessment of CD171-directed CAR T cell adoptive therapy for childhood neuroblastoma: CE7 epitope target safety and product manufacturing feasibility." Clin Cancer Res 2017, 23:466-477.