• sense clinically
  • think mechanistically
  • act interdisciplinarily
  • treat innovatively

PD Dr. med. Annette Künkele

Charité - Universitätsmedizin Berlin
Campus Virchow Klinikum
Department of Pediatrics, Division of Oncology and Hematology
Augustenburger Platz 1
13353 Berlin

Tel: +49 30 450 566 132

kinderonkologie.charite.de/en/metas/person_detail/person/address_detail/kuenkele-1/

 

Scientific Scope

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.

Selected References

  • Toews KGrunewald LSchwiebert SKlaus AWinkler AAli SZirngibl F, Astrahantseff K, Wagner DL, Henssen AG, Deubzer HE, Schulte JH, Ochsenreither S, Eggert A, Künkele ACentral memory phenotype drives success of checkpoint inhibition in combination with CAR T cells. Mol Carcinog. 2020 Jul;59(7):724-735. doi: 10.1002/mc.23202. Epub 2020 Apr 25. PMID: 32333465. PubMed
  • Ali SToews KSchwiebert SKlaus AWinkler AGrunewald L, Oevermann L, Deubzer HE, Tüns A, Jensen MC, Henssen AG, Eggert A, Schulte JH, Schwich E, Rebmann V, Schramm A, Künkele ATumor-Derived Extracellular Vesicles Impair CD171-Specific CD4+ CAR T Cell Efficacy. Front Immunol. 2020 Mar31;11:531. doi: 10.3389/fimmu.2020.00531. PMID: 32296437; PMCID: PMC7137471. PubMed
  • Koche RP, Rodriguez-Fos E, Helmsauer K, Burkert M, MacArthur IC, Maag J, Chamorro R, Munoz-Perez N, Puiggròs M, Dorado Garcia H, Bei Y, Röefzaad C, Bardinet V, Szymansky A, Winkler A, Thole T, Timme N, Kasack K, Fuchs S, Klironomos F, Thiessen N, Blanc E, Schmelz K, Künkele A, Hundsdörfer P, Rosswog C, Theissen J, Beule D, Deubzer H, Sauer S, Toedling J, Fischer M, Hertwig F,
  • Schwarz RF, Eggert A, Torrents D, Schulte JH, Henssen AG. Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma. Nat Genet. 2020 Jan;52(1):29-34. doi: 0.1038/s41588-019-0547-z. Epub 2019 Dec 16. Erratum in: Nat Genet. 2020 Feb 27;: PMID: 31844324;  PubMed
  • Andersch L, Radke J, Klaus A, Schwiebert S, Winkler A, Schumann E, Grunewald L, Zirngibl F, Flemmig C, Jensen MC, Rossig C, Joussen A, Henssen A, Eggert A, Schulte JH, Künkele ACD171- and GD2-specific CAR-T cells potently target retinoblastoma cells in preclinical in vitro testing. BMC Cancer. 2019 Sep9; 19(1):895. doi: 10.1186/s12885-019-6131-1. PubMed PMID: 31500597; PubMed
  • Künkele A, Brown C, Beebe A, Mgebroff S, Johnson AJ, Taraseviciute A, Rolczynski LS, Chang CA, Finney OC, Park JR, Jensen MC. Manufacture of Chimeric Antigen Receptor T Cells from Mobilized Cyropreserved Peripheral Blood Stem Cell Units Depends on Monocyte Depletion. Biol Blood Marrow Transplant. 2019 Feb;25(2):223-232. doi: 10.1016/j.bbmt.2018.10.004. Epub 2018 Oct 10. PubMed
  • Gottlieb A, Althoff K, Grunewald L, Thor T, Odersky A, Schulte M, Deubzer HE, Heukamp L, Eggert A, Schramm A, Schulte JH, Künkele A. RITA displays anti-tumor activity in medulloblastomas independent of TP53 status. Oncotarget. 2017 Apr 25;8(17):27882-27891. doi: 10.18632/oncotarget.15840. PubMed
  • Künkele A, Taraseviciute A, Finn LS, Johnson AJ, Berger C, Finney O, Chang CA, Rolczynski LS, Brown C, Mgebroff S, Berger M, Park JR, Jensen MC. 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 Jan 15;23(2):466-477. doi: 10.1158/1078-0432.CCR-16-0354. Epub 2016 Jul 7. PubMed
  • Künkele A, Wilm J, Holdt M, Lohmann D, Bornfeld N, Eggert A, Temming P, Schulte JH. Neoadjuvant/adjuvant treatment of high-risk retinoblastoma: a report from the German Retinoblastoma Referral Centre. Br J Ophthalmol. 2015 Jul;99(7):949-53. doi: 10.1136/bjophthalmol-2014-306222. Epub 2015 Jan 12. PubMed
  • Künkele A, Johnson AJ, Rolczynski LS, Chang CA, Hoglund V, Kelly-Spratt KS, Jensen MC. Functional Tuning of CARs Reveals Signaling Threshold above Which CD8+ CTL Antitumor Potency Is Attenuated due to Cell Fas-FasL-Dependent AICD. Cancer Immunol Res. 2015 Apr;3(4):368-79. doi: 10.1158/2326-6066.CIR-14-0200. Epub 2015 Jan 9. PubMed