A new study has found that genetically modified chimeric antigen receptor T cells (CAR T cells) targeting the KIT-receptor (CD117) may be a new therapeutic option for treating advanced forms of systemic mastocytosis (SM).

The study results were presented in a poster session at the European Hematology Association 2023 Hybrid Congress in June in Frankfurt, Germany.

“Our previous work demonstrated that CD117 (KIT-receptor) positive human acute myeloid leukemia [AML] are efficiently eradicated by anti[1]CD117 CAR T-cells in vitro and in vivo,” the authors wrote. “This study aims at employing CAR T-cells targeting human CD117 in preclinical models of SM and testing the efficacy of this approach in vitro and in vivo as a novel therapy option for SM.”

The authors cultured mast cell lines with and without the KIT D816V mutation, KIT D816V-positive SM patient-specific iPS cell-derived mast cells, and SM patient-derived mast cells in vitro with anti-CD117 CAR T cells. In addition, they treated mast cell line (ROSA KIT D816V)-engrafted immunodeficient mice with anti-CD117 CAR T cells and with control T cells.

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CAR T cell activation and proliferation, and cytokine production, were measured in the cultured cells, and peripheral blood, bone marrow, liver, and spleen were assessed for mast cell infiltration in the mouse model.

The results revealed that after 24 hours of in vitro culturing, the CAR T cells proliferated and produced proinflammatory and activation-stimulating cytokines including interleukin-2, which effectively killed the tumor cells compared with those treated with control T cells.

The injection of anti-CD117 CAR T cells in the mice resulted in a significant reduction of in vivo tumor cells and increased survival of the mice.

The authors caution that there will likely be collateral damage to healthy hematopoietic stem and progenitor cells given the efficiency of CAR T cells, but they are encouraged to explore a possible therapeutic window for anti-CD117 immunotherapy in advanced SM.


Kaiser A, Myburgh R, Volta L, et al. Human CD117 as an immunotherapeutic target in preclinical models of advanced systemic mastocytosis. Presented at: European Hematology Association (EHA) 2023 Hybrid Congress, Frankfurt, Germany; June 8, 2023.