Abstract
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-α) 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-α, 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/γc− (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-α 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-α (P = 0.022). Furthermore, unlike CB mononuclear cells or peripheral blood mononuclear cells (PBMC), CD56+CB-CIK cells, alone or stimulated with hIFN-α, 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-α 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.
Disclosure of Conflicts of interest: The authors declare no potential conflicts of interest.
This work was supported by grants from the Fonds de la Recherche en Santé du Québec (FRQS) (Fonds de recherches en medecine transfusionnelle, en greffe et en biovigilance 2010–2013), the Fondation du CHU Sainte-Justine and the Fondation Charles Bruneau. LD received a scholarship from the Fondation de l’Hôpital Sainte-Justine/Fondation des Étoiles and a doctoral studentship from the Department of Microbiology and Immunology, University of Montreal. EH is a scholar of the FRQS.