Human interferon-alpha increases the cytotoxic effect of CD56+ cord blood-derived cytokine-induced killer cells on human B-acute lymphoblastic leukemia cell lines

Background aims. Cytokine-induced killer (CIK) cells may represent a promising immunotherapy for the treatment of children with relapsing B-lineage acute lymphoblastic leukemia (B-ALL) following hematopoietic stem cell transplantation (HSCT). Therefore, we investigated the possibility of combining adoptive immunotherapy with CIK cells and human interferon-alpha (hIFN-alpha) in order to potentiate the cytotoxicity of CIK cells against B-ALL. Methods. Cord blood-derived CIK (CB-CIK) cells were differentiated, stimulated with phosphate-buffered saline (PBS) or hIFN-alpha, and tested for cytotoxic activity. We tested the anti-leukemic and graft-versus-host disease (GvHD) effects of CB-CIK cells in a human xenograft NOD/SCID/gamma c(-) (NSG) mouse model. Results. Bulk CB-CIK cells showed very moderate cytotoxic activity while the subpopulation of CD56(+) CB-CIK cells showed significant cytotoxic activity against B-ALL cells. hIFN-alpha significantly augmented the cytotoxicity of CD56(+) CB-CIK cells in vitro and induced signal transducer and activator of transcription-1 (STAT1) phosphorylation. In addition, CD56(+) CB-CIK cells could delay mouse mortality significantly in vivo, and this effect was enhanced significantly by hIFN-alpha (P = 0.022). Furthermore, unlike CB mononuclear cells or peripheral blood mononuclear cells (PBMC), CD56(+) CB-CIK cells, alone or stimulated with hIFN-alpha, caused either no GvHD or mild GvHD, respectively, when injected into sublethally irradiated NSG mice. Conclusions. CD56(+) CB-CIK cells are effective cytotoxic agents against human B-ALL cell lines in vitro and possess anti-leukemic activity that is potentiated by hIFN-alpha in an NSG mouse model in vivo. These pre-clinical data support the testing of this immunotherapeutic approach in the clinic for the treatment of B-ALL