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Poster Display session

405 - Anti-human CD117 CAR T-cells efficiently eliminate hematopoietic stem and CD117-positive AML cells


14 Dec 2018


Poster Display session


Renier Myburgh


Annals of Oncology (2018) 29 (suppl_10): x11-x16. 10.1093/annonc/mdy485


R. Myburgh1, J. Kiefer2, N. Russkamp1, A. Simonis1, S. Pfister1, C. Magnani1, M. Wilk1, A. Müller1, M. van den Broek3, B. Becher2, D. Neri4, M.G. Manz5

Author affiliations

  • 1 Department Of Hematology And Oncology Division Of Hema, UniversityHospital Zürich, 8091 - Zurich/CH
  • 2 Department Of Chemistry And Applied Biosciences, Institute of Pharmaceutical Sciences, 8093 - Zürich/CH
  • 3 Institute Of Experimental Immunology, University of Zurich, 8057 - Zurich/CH
  • 4 Department Of Chemistry And Applied Biosciences, ETH Zürich, 8093 - Zürich/CH
  • 5 Department Of Hematology And Oncology, Universitätsspital Zürich, 8091 - Zürich/CH


Abstract 405


Acute Myeloid Leukemia (AML) is a clonal disease of the hematopoietic system. Disease relapses are common with current treatment approaches. As an alternative, immunological eradication of leukemic cells by adoptively transferred chimeric-antigen receptor T-cells (CAR T-cells) might be considerably more efficient. To date, however, the search for AML-specific surface antigens has remained largely elusive. To circumvent this problem, we propose to target the stem cell antigen c-Kit (CD117) that is expressed by physiological HSPC as wells as by leukemic blasts in > 90% of AML patients.


A lentiviral vector was generated expressing a second generation CAR targeting human CD117 followed by a T2A sequence and RQR8 as selection marker and depletion gene (surface expression of CD34 and CD20 epitopes).


In vitro, CAR T-cells eliminated over 90% of CD117high leukemia cell lines within 24 hours. In long–term cytotoxicity assays (45d), only CD117low cells were able to escape CAR-mediated killing compared to CD117high and CD117intermediate cells which were not able to survive. Anti-CD117 CAR T-cells effectively depleted >90% of lin-CD117+CD34+CD38+ and >70% of lin-CD117+CD34+CD38- cells from healthy bone marrow in vitro. Similarly, >70% of patient derived leukemic blasts were eliminated by autologous anti-CD117 CAR T-cells within 48 hours. In vivo, immunodeficient mice were engrafted with umbilical cord blood derived CD34+ cells. A single injection of 2x106 anti-CD117 CAR T-cells resulted in > 90% depletion of CD117+ cells in the bone marrow within 6 days. Finally, humanized mice transplanted with bone marrow from AML patients were treated with autologous CAR T-cells. At 6 weeks after injection of CAR T-cells, >98% of hu-CD45 CD117+ cells were depleted in the bone marrow.


We provide proof of concept for the generation of highly-potent CAR T-cells against CD117. Anti-CD117 CAR T-cells exhibit high cytotoxic activity against CD117+ cell lines as well as primary healthy HSPC and patient AML cells in vitro and in vivo in murine xenograft models. Strategies for the complete elimination of CAR T-cells (immunologic or small molecule based) are required before translation of this approach to the clinical setting.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

University Hospital Zurich.


PROMEDICA stiftung, URPP University of Zuric, Krebsliga Schweiz.


All authors have declared no conflicts of interest.

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