CIK cells from recurrent or refractory AML patients can be efficiently expanded in vitro and used for reduction of leukemic blasts in vivo

Abstract

Autologous cytokine-induced killer (CIK) cell transfusion may prevent tumor relapse in acute myeloid leukemia (AML). This study investigated whether CIK cells from recurrent or refractory AML patients with high peripheral leukemia cell burdens could be expanded to a clinically usable number, and it further evaluated the antitumor potentials in vitro and in vivo. The numbers and phenotypes of CIK cells expanded from nine AML patients and 10 healthy donors were compared. Cytotoxicity (against K562 and U937 cell lines) and cytokine secretion (interleukin-2, interferon-γ, tumor necrosis factor-α and vascular endothelial growth factor) were tested for AML-derived and healthy donor-derived CIK cells and fresh peripheral blood mononuclear cells from healthy donors. Importantly, we assessed the therapeutic effects of autologous CIK cell infusions in two patients with AML. The proportions of CD3(+)and CD3(+)CD56(+) CIK cells from patients with AML were similar to those from healthy donors, and the number of CD3(+)CD56(+) cells in AML-derived CIK cells was expanded approximately 1,020-fold. Phenotype analyses with flow cytometry showed that the leukemic cells were gradually eliminated during the process of CIK cell preparation to an almost undetectable level. Although the cytotoxic effect of AML-derived CIK cells was equivalent to that of healthy donors, AML-derived CIK cells had a significantly higher cytokine-secreting capacity. In clinical treatment, the leukemia burden in the peripheral blood of one patient was dramatically decreased after four transfusions within 4 months. CIK cells can be efficiently expanded in vitro from patients with recurrent or refractory AML and may be used for reduction of leukemic blasts in vivo.